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THE GENETICS

REVDLUTIDN
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THE GENETICS
REVDLUTIDN
HISTDRY, FEARS, AND FUTURE
DF A LIFE- ALTERING SCI ENCE
R D S E M. MD R G A N
Greenwood Press
Westport, Connecticut London
Library of Congress Cataloging4n-Publication Data
Mor gan, Rose M. , 1935
The genetics revol ut i on : history, fears, and future of a life-altering
science / Rose M. Mor gan,
p. cm.
Includes bibliographical references and i ndex.
ISBN 0- 313- 33672- 5 (alk. paper)
1. Medi cal genet i csResearchMoral and ethical aspects. 2. Genetic
engi neeri ngMoral and ethical aspects. 3. Human cl oni ngMoral and
ethical aspects. I. Title.
[ DNLM: 1. Genetics, Medi cal et hi cs. 2. Genetics, Medi cal t rends.
3. Ethics, Medi cal . 4. Genet i c Techni queset hi cs. 5. Genet i c Techni ques
t rends. 6. Genome, Human. 7. St em Cells. QZ 50 M849g 2006]
RB155. M673 2006
174.2' 8dc22 2005019205
British Li brary Cataloguing in Publication Dat a is available.
Copyri ght 2006 by Rose M. Mor gan
All rights reserved. No p or t i on of this book may be
reproduced, by any process or t echni que, wi t hout t he
express wri t t en consent of t he publisher.
Library of Congress Catalog Card Number : 2005019205
ISBN: 0- 313- 33672- 5
First publ i shed in 2006
Gr eenwood Press, 88 Post Road West, West p or t , CT 06881
An i mpri nt of Gr eenwood Publishing Gr oup, Inc.
www. greenwood. com
Pri nt ed in t he Uni t ed States of Ameri ca
The paper used in this book compl i es wi t h t he
Permanent Paper St andard issued by t he Nat i onal
Informat i on St andards Organi zat i on (Z39.48-1984).
10 9 8 7 6 5 4 3 2 1
Every reasonable effort has been made t o trace t he owners of copyright materials in
this book, but in some instances this has proven impossible. The aut hor and
publ i sher will be glad t o receive i nformat i on leading t o mor e compl et e
acknowl edgment s in subsequent printings of t he book and in t he meant i me ext end
their apologies for any omi ssi ons.
CDNTENTS
Preface
Part I. On the Brink of Altering Life
1. Recombining DNA Molecules
2. Splicing Life: Technological Revolution or Pandora' s Box?
3. The Book of Life: The Human Genome Project
Part II. Beauty and the Beast
4. Laboratory Babies: New Biology, Old Morality
5. The Warnock Report
Part III. Fighting to Save a Gene Pool
6. The Human Genome Diversity Project
7. The HGDP Debate
Part IV. Threading an Ethical Needle
8. Stem-cell Research
9. A Major Decision
Part V. To Clone or Not to Clone: That Is the Question
10. Reproductive Cloning
11. Cloning a Human
vii
1
3
19
35
53
55
71
91
93
105
129
131
145
157
159
175
CDNTENTB
Notes 193
Bibliography 203
Index 211
PREFACE
The discovery of the structure of DNA by Crick and Watson,
with all its biological implications, has been one of the major sci-
entific events of the 20th century
Sir Lawrence Bragg, Nobel Prize recipient
and director of the Cavendish Laboratory at
Cambridge University, in the foreword to
Watson's book, The Double Helix
Humanity has much to learn from history In this context we are reminded that
the rise of modern-day DNA technology owes its origin to the many scientific
events that occurred over a relatively long period of time.
Despite past successes of the various DNA technologies, however, the public
has always been uneasy as to what scientists should and can do. Today, as in past,
the world struggles with an ability to thread its way through an ethical minefield
surrounding various genetic issues.
The scientific method had its beginnings in the fifteenth and sixteenth cen-
turies. However, systematic experimentation in the laboratory was not carried
out until the seventeenth century. Even in the early nineteenth century science
and technology were not included in the mainstream of major achievements.
Rather, it was a time when questions were posed about evolution, the purpose of
advancement, and the nature of human beings.
It was a different story from the mid-nineteenth century to end of the twenti-
eth century, when there were decades of enormous development in scientific
knowledge. In 1865, Gregor Mendel, an Austrian monk, was credited as the first
to lay the mathematical foundation of the science of genetics. Later he became
known as the "Father of Genetics." Charles Darwin' s revolutionary ideas on evo-
lution were finally recognized during this period in time and there followed a daz-
zling burst of genetic information.
In 1931 it took Aldous Huxley, the brilliant English author, only four months
to write his most famous novel, Brave New World, Huxley used Brave New World
as a warning against the misuse of science and about the consequences of a soul-
less technology. During this time there were significant political, philosophical,
and economic changes taking place in the United States and Europe. It was a time
when Adolf Hitler and the Nazi party came into power in Germany, but before
Joseph Stalin's Bolshevik Revolution in the Soviet Union and before Benito
Mussolini led an authoritarian, fascist Italy.
In April 1953, two young scientists, James Watson and Francis Crick, eluci-
dated the double-helical, spiral-staircase structure of DNA that became the key
to the technology of life. The dividends that resulted from Watson and Crick' s
discovery are too numerous to count, and today in laboratories worldwide scien-
tists use the information from that scientific milestone.
By 1970 Watson and Crick' s discovery had been known for seventeen years
and a new term, recombinant DNA technology (also known as gene splicing and
genetic engineering), was introduced into our vocabularies. What it meant for so-
ciety was a second mobilization of biology. It permitted the transfer of genetic
material not only across species lines but out of the animal kingdomfor exam-
ple, transferring a human' s insulin gene into bacteria. However, the new DNA
technology had important consequences because for the first time it gave humans
control over various possibilities for curing diseases.
The first child ever conceived outside a mother' s body under controlled
conditions, Louise Brown, was born on July 25, 1978, in Oldham, England.
Drs. Robert Edwards and Patrick Steptoe, English physicians who performed the
IVF procedure, had taken it as their duty to satisfy the natural desire of every
couple to have a child, by natural or artificial means. However, behind the beauty
of Louise Brown's unique creation there lurked a beast in the form of nightmares
and concerns voiced by ethicists, philosophers, theologians, lawyers, and physi-
cians. These individuals, on both sides of the Atlantic, warned that the medical
miracle of IVF indicated the arrival of unort hodox medicine as forecast in Brave
New World.
In response to the heated controversy over IVF, the British government com-
missioned Dame Mary Warnock, of Girton College, Cambridge University, to
form a committee to study recent and potential developments in medicine and
science related to human fertilization and embryology. Warnock' s Committee of
Inquiry into Human Fertilization and Embryology eventually issued sixty-four rec-
ommendations.
Progress in elucidating the molecular basis of disease at the genetic level con-
tinued to progress at a rapid rate. This was due largely to the Human Genome Pro-
ject (HGP), the largest and most expensive scientific study conducted since the
Apollo project and the race to send a human to the moon. For the first time, there
was tangible hope for the control of most genetic diseases and even some degener-
ative ones. In June 2001 the HGP was completed, ahead of the April 23, 2003,
deadline that marked the fiftieth anniversary of Watson and Crick's discovery.
PREFACE
VII
In 1991 a group of prominent Bay Area human geneticists and molecular bi-
ologists proposed to the scientific community that a five-year international study,
known as the Human Genome Diversity Project (HGDP), be undertaken to deter-
mine variation in the human genome. The well-intended study was to be an effort
to collect and preserve DNA samples from a part of the world's 4,000-8,000 en-
dangered populations and was designed to give insights into the origins of ancient
populations. However, from its beginnings, indigenous groups voiced concerns
about patenting human genes, diversion of funds, the potential for biological war-
fare, violation of human rights, informed consent, and biopiracy. Almost from the
beginning, various indigenous groups called for a halt of the HGDP.
The first authentic reproductive cloning made news on July 5, 1996, when the
cloned lamb named "Dolly" (after the entertainer Dolly Parton) was born near
the Roslin Institute in Edinburgh, Scotland. Essentially her mother' s physical
twin, Dolly was in all appearances a normal sheep, the first-ever cloned animal
from a specialized (differentiated) adult cell.
On January 6, 1998, Chicago physicist Richard Seed shocked the world by
announcing plans to clone a human, setting off an emotionally charged national
debate. As a result, U.S. president Bill Clinton immediately renewed efforts for
federal legislation to outlaw both public and private attempts to clone a human.
Several bills were introduced to outlaw cloning of any kind, opponents arguing
that humankind would be reduced to genes. Supporters countered that therapeu-
tic cloning/stem-cell research had the potential to cure many major illnesses.
On August 9, 2002, in a prime-time speech to the nation, President George
W. Bush gave the go-ahead for limited federal funding on existing embryonic
stem-cell research. Attempting to thread an ethical needle, the president' s deci-
sion was a definite compromise that allowed him to address concerns about the
willful destruction of potential human life, while giving hope to those suffering
from horrible diseases that might be cured by embryonic stem-cell research.
Like the arts, DNA science and thought have experienced substantial politi-
cal pressures. The Qenetics Revolution: History, Tears, and Future of a Life-Altering
Science is a book that will confront you, the reader, with alternative points of
view on complex and sensitive genetic issues. However, we are reminded that
moral and ethical genetic issues are continually changing and what may not be
moral and ethical today could well be acceptable in the near future. This may be-
come more pronounced as the skills and expertise of scientists and physicians
become more advanced.
As you read the book you will have a deeper understanding of some of the
genetic issues that surround us today, as well as those of yesterday. In the twenty-
first century, the success of the new DNA technologies will transform the course
of society's thought and activity, bringing a heightened degree of social awareness
and compassion. The Chinese have a pertinent saying: "May you live in interest-
ing times." That we do!
PREFACE
IX
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PART I
On the Brink of
Altering Life
By 1970 the double-helix structure of DNA had been known for seventeen years.
In the early 1970s the ability to recombine DNA molecules became the single
most important biological tool developed. The Human Genome Project became a
worldwide effort to analyze the structure of DNA and to determine the location
of the genes. Ethical and legal issues were discussed in almost every church in the
United States and throughout the entire world. As a result, the 1970s represented
a decade of intense scientific controversy.
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1
RECDMBI NI NG DNA
MDLECULES
You can stop splitting the atom; you can stop visiting the moon;
you can stop using aerosols; you may even decide not to kill en-
tire populations by the use of a few bombs. But you cannot recall
a new form of life.
Erwin Chargaff, biochemistry professor at
Columbia University, in a 1976
letter to the editor of Science
Late one winter day in 1953, two excited young men, James D. Watson, twenty-
four, and Francis Crick, thirty-six, ran out of Cambridge University's Cavendish
Laboratory and into the Eagle, a pub traditionally frequented by Cambridge scien-
tists. As the two talked intensely over drinks, friends stopped to learn the reason
for the excitement. At the time, Crick burst out exultantly, "We have discovered
the secret of life."
1
On that day, Watson and Crick, until then unknown outside the Cavendish
Laboratory, had finally worked out the now famous double-helical, spiral-staircase
structure of DNA. Their discovery was based in part on the sharp X-ray diffrac-
tion photographs of DNA provided by Maurice Wilkins and Rosalind Franklin,
coworkers at King's College, London.
2
On April 25, 1953, Watson and Crick announced in the prestigious British
journal Nature their spectacular discovery of the double helical structure of
DNA, considered the most important biological work of the twentieth century
and the key to the technology of life. The discovery stimulated dramatic new re-
search and changed forever understanding of the gene, inheritance, and natural
selection.
3
THE GENETI CS REVDLUTI DN
Since the discovery by Watson and Crick the study of DNA has become the
focal point of research examining normal and abnormal biological processes.
Today, more than 5,000 human genetic diseases are known to exist and a major
effort of modern molecular biology is to identify the defects in DNA that result
in pathologic states.
Recombining DNA Molecules
By 1970 Watson and Crick's double-helix structure of DNA had been known for
seventeen years. In the early 1970s, a new term was introduced to our vocabularies
recombinant DNA (rDNA), also called genetic engineering or gene splicing. This
was a unique technology that allowed a new and more precise kind of gene manip-
ulation. What was not known at that time, but was discovered shortly thereafter,
was that segments of the DNA genetic code could be spliced together precisely
from virtually any source to recode a cell's genetic information.
Recombinant DNA technology permitted the transfer of genetic material not
only across species lines but out of the animal kingdomfor example, a human' s
insulin gene into bacteria. The perfected rDNA technique made it possible to iso-
late genes, changes in the genes and how they were expressed and, together with
other techniques, to insert the genes into the whole organism.
Recombinant DNA technology was followed by the isolation of bacterial en-
zymes called "restriction endonucleases" ("restriction enzymes") that could
splice together DNA from different species. This ability to recombine the DNA
molecule to create novel life forms was the single most important new biological
tool developed in the 1970s. As a result of rDNA technology, the 1970s took its
place as a discrete historical epoch in the United States, much like the Great De-
pression or the Roaring Twenties.
4
A Decade of Intense Science Controversy
Controversy is nothing new to scientists. It is absolutely counter to scientists to
take anything on faith, so it was not unusual that when scientists were developing
rDNA techniques that a vicious controversy erupted. The debate within the com-
munity of biological and social scientists became one of the largest controversies
in recent scientific history.
The rDNA controversy actually got into full swing in 1971 when scientists
postulated, devised, and began to refine a unique technique to splice and recom-
bine segments of DNA between cells from different species of living things, re-
gardless of the sexual compatibility of the organisms or the distance of their
evolutionary relationship.
5,6
The debate over rDNA was passionate and with on-
going power struggles erupting on all sides, the scientific community became
more aggressive and highly competitive, taking control and manipulating genes
through rDNA. Subsequently, this led to the diagnosis, treatment, prevention,
and potential cure of thousands of different diseases. Quite literally, it marked a
watershed for those who were concerned with rDNA.
7
A
RECDMBI NI NG DNA MDLECULES
As the debate intensified and extended among those not only in science but
in politics and technology as well, many professional relationships were hurt
beyond repair. On one side, rDNA technology presented itself as a new and in-
novative technology. On the other hand, it presented itself as an evil Frankenstein
monster, frightening and terrifying even to those who believed in it.
Clearly, at the center of the rDNA controversy were potential biohazards and
risk. Many worried about the hazards of novel genetically-engineered organisms,
adequate safety precautions, and what was being done to safeguard the populus.
As a result, fear and hostility toward rDNA technology became rampant in the
United States.
There were numerous issues relevant to genetic manipulationfor example,
the possibility of some ecological disruption; the ethics of human genetic inter-
vention; the argument over regulatory policy; and the possibility of using rDNA
technology for biological warfare.
8
It was not until 1977 that the U.S. government
really became involved with safety issues.
Opponents argued that the production of rDNA was a new evolutionary
event, one that would violate natural barriers and result in the production of new
species.
9
Some opposed rDNA technology for religious beliefs, ethical concerns,
and conflicting ideology. Others had specific fears of nuclear wastes, chemical
and biological pollution of the earth and its atmosphere, and evil, self-serving sci-
entists and physicians much like those depicted in Aldous Huxley's Brave New
World. Opponents of rDNA technology repeatedly referred to the period of nu-
clear arms to emphasize their fears.
History has shown rDNA technology to be neither good nor bad. Whereas
there has been no definitive evidence to show that rDNA is a biohazard, neither
has there been any evidence to show that it has not been a biohazard. Many
thousands of rDNA experiments, in thousands of laboratories over three de-
cades, have not produced hazards. Even the original experiments, which took
apart a DNA molecule and put segments of it back together again, have not
appeared hazardous.
10
Yet, despite decades of safety, there are still those who be-
lieve strongly that the technology should have been stoppedor at least slowed
down.
As new and increasingly more sophisticated rDNA technology surfaced, the
rDNA controversy gradually came to a head. Government-sponsored groups,
federal and local, played key roles in settling the rDNA debate, as well as the
complex sociological, political, and psychological factors that impinged upon sci-
ence. Discussions centered mostly around positions of strong public health and
safety standards, as well as the future of genetically-engineered weapons, some in
the hands of foreign dictators.
In 1970 a team of Harvard scientists succeeded in isolating a DNA fragment.
However, two of the scientists on the team felt so strongly that genetic research
would be used for evil purposes that they quit the Harvard team. Dr. James
Shapiro, one of the scientists who quit, gave three major reasons for doing so.
First, he felt that his research would be put to evil uses by government and large
corporations that controlled science.
11,12
He also believed that the research would
lead to political oppression and the creation of so-called inferior subclasses of be-
ings based on genetic classification.
13
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THE GENETI CS REVDLUTI DN
Second, Shapiro said he wouldn' t work where he didn' t have a say in what
scientists do. Third, he felt that the U.S. problems needed political solutions
more urgently than they did scientific ones. Shapiro, who was twenty-six years
old at the time, said he felt compelled to quit genetic engineering research to try a
career in politics; his political ideology was "having all of society decide what
work scientists will do."
14
The other researcher who decided to quit was Dr. Jonathan Beckwith, age
thirty-three. Seeking opportunities in other areas of genetics, he later became a
leader of a group called Science for the People, a radical congregation that believed
genetics would "diminish awareness of the social and political causes of health
problems" and would allow genetics to be used as a tool of social control against
"the people." In effect, both Shapiro and Beckwith reportedly quit because they
wanted the genetic research they were involved in to be stopped. Interestingly,
their quitting had little effect on further research by other investigators; nor did it
make any significant impression on public opinion.
Many of the strongest opponents of rDNA research, who included Beck-
with, Shapiro, and Nobel Prize winner and Harvard scientist George Wald, along
with others from the Science for the People organization, were already firmly
established on the intellectual American left. Science for the People argued
against permitting rDNA research in the United States on the grounds that it
was intrinsically dangerous to humans and nature and that scientists were only
concerned with their immediate, personal advantage.
15
Emphasis on technologi-
cal solutions to health problems, Science for the People declared, would result in
diversion or distraction from other goals that were essential for real social
progress.
16
In 1971 Robert Pollack at the Cold Spring Harbor Laboratory Tumor Virus
Workshop began to raise safety issues associated with rDNA technology. That
same year, Paul Berg, a professor at Stanford University who later won a Nobel
Prize for his role in developing rDNA, and Janet Mertz (a graduate student in
Berg's lab), attempted to produce a hybrid by using two different viruses, a mam-
malian t umor virus called SV40 (simian virus 40) and lambda (a virus of E. coli
bacteria, the common bacteria of the human intestinal tract). However, while
working on the project, Berg and his team became concerned that the experiment
might possibly produce an organism that could carry cancer genes (oncogenes),
with the potential ability to spread epidemics of cancer.
During the summer of 1971, Mertz described the experiment to the Cold
Springs Harbor Seminar. In her talk, Mertz acknowledged that even though E. coli
flourished in the human intestine and was relatively harmless, SV40 posed serious
problems since it was a suspected carcinogen. Seminar participants posed the ques-
tion to Mertz: If this kind of genetically-engineered organism were to escape from
the lab, could it infect people and increase their chances of developing cancer?
At the time, scientists believed that there were both known and unknown
risks in genetic research. Later, however, it was shown that the specific experi-
ment Mertz described would have interrupted the reproduction genes of lambda
and the products would have constituted no danger. However, this was not
known at the time and, as a result, the concerns of conference participants were
taken very seriously.
6
RECDMBI NI NG DNA MDLECULES
Asilomar I Conference
The worries of Berg, Mertz, and others resulted in an assembly of great scientists
at the Conference on Biohazards in Biological Research (designated the Asilomar
1 Conference), held at the Asilomar Conference Center in Pacific Grove, Califor-
nia, on January 22-24, 1973. Conference attendees held important discussions
over safety issues of rDNA and eventually came to substantial agreement as to
what could and should be done.
However, before the results of the conference could lead to action, late in
1973 Stanley Cohen of Stanford University and Herbert Boyer of the University
of California at San Francisco chemically cut a gene out of a cell from Xenopus
laevis (the common toad) and spliced the gene into the microbe E. coli.
11
Cohen
and Boyer succeeded in getting the microbe to express the toad gene exactly, as if
it were one of its own, and in so doing they were given credit for discovering re-
combinant DNA (rDNA). Some hailed the discovery as a huge step for molecular
genetics; others feared it had opened Pandora' s box.
Because of the potential dangers of rDNA research, members of the Confer-
ence placed a moratorium on two phases of rDNA research. First, they stopped
the introduction of antibiotic-resistant genes or bacterial toxin genes into bacte-
ria. Second, they stopped the introduction of DNA from t umor viruses or any
other animal viruses into reproducing DNA organisms.
18
Gordon Research Conference on Nucleic Acids
The Asilomar I Conference was followed on June 11-15, 1973, by the Gordon
Research Conference on Nucleic Acids, a gathering of some of the world' s great-
est scientists at New Hampton, New Hampshire. Many still consider this gather-
ing the birth of the rDNA controversy. The goal of Gordon Conferences has
always been to stimulate research in universities, research foundations, and in-
dustrial laboratories.
Chaired by Paul Berg and sponsored by the prestigious National Academy of
Science, the informal Gordon Conference was designed to place a great deal of
emphasis on informal discussions for the exchange of new, as well as published,
scientific rDNA information. Two kinds of scientific concerns were expressed at
the meetingspecific fears of identifiable risks associated with specific experi-
ments, and general fears of cataclysmic dangers if the rDNA research were pur-
sued. Scientists at the conference expressed concerns that parts of DNA from
disparate organisms could be hooked together in a test tube (in vitro) and then
reinserted into a host organism.
19
Not surprisingly, definite political lines were drawn among the 143 attendees
at the conference. Younger scientists were more aggressive, raising broad socially
oriented questions, with the exception of those scientists actively involved in
rDNA research. In contrast, conservative older scientists generally favored re-
stricting rDNA research.
One participant at the Gordon Conference was Edward Ziff, a respected scien-
tist who called for discussion of rDNA biohazards. Ziff had two specific concerns.
v
THE GENETI CS REVDLUTI DN
The first concern was with the production of DNA hybrids that were synthesized
by recombining parts of DNA. His second concern was that large-scale produc-
tion and isolation of potential cancer-causing viruses could become a reality and
that laboratory personnel might contract cancer from the t umor viruses with
which they were working. Because of these concerns, Ziff called for the establish-
ment of better containment facilities for rDNA research.
Other scientists attending the Gordon Conference drew parallels between
rDNA research and the early years when biological weapons and atomic energy
were used and the secrecy that had surrounded the buildup of nuclear arms. Re-
gardless of their stand on the r DNA issue, however, conference attendees over-
whelmingly voted to send a letter stating their concerns to the National
Academy of Sciences, with a request that the letter be openly published in the
journal Science. Paul Berg was elected to head the Assembly of Life Sciences of
the National Research Council, composed of distinguished scientists in the
field.
Concern at the meeting also centered around publicizing the issue. A mora-
torium was proposed on the introduction of new antibiotic resistance or bacter-
ial toxin genes into bacteria that did not normally carry these genes, and on the
introduction of DNA from t umor viruses of other animal viruses into au-
tonomously reproducing DNA elements.
20
Members of the Gordon Conference proposed a number of recommenda-
tions, and on September 21, 1973, a letter, carefully worded and comprehensible
to scientists in the field, was published in full in Science. The letter, coauthored by
Maxine Singer and Dieter Soil, cochairs of the 1973 Gordon Conference, ex-
pressed sentiments of Conference participants on the potential hazards of rDNA
techniques and recommended to laboratory scientists a few specific types of ex-
periments.
21
As a result of the Gordon letter, molecular biology became more
widely known.
On April 17, 1974, the first meeting of a free-standing committee convened.
Attended by highly regarded scientists including Nobel laureate David Baltimore,
the conference was directed to assess the current status of rDNA technology
Committee members agreed on two items that should be accomplished. First, it
would determine what kind of experiments (if any) should be deferred. Second,
it would determine the kinds of experiments that would be allowed in which ani-
mal DNA fragments were inserted into bacteria.
At the meeting, some scientists favored a moratorium. However, most atten-
dees agreed that scientific inquiry was needed and that constraints of any kind
were a transgression of that inalienable right. After considerable discussion, the
following conclusions were reached: First, major efforts would be taken to keep
decision making within the professional boundaries of the scientific community.
Second, little effort would be made to outline the long-term impacts of rDNA
techniques in the industrial sector. Third, it would be decided as to who should
have monopoly on rDNA procedures.
In June 1974 David Baltimore read a draft of a letter to members at the Cold
Spring Tumor Virus meeting where he announced that parts of DNA from dis-
parate organisms could be hooked together in the test tube and then reinserted
into a host organism.
22
s
RECDMBI NI NG DNA MOLECULES
The Berg Letter
On July 26, 1974, a letter, composed by Berg and ten other internationally fa-
mous molecular scientists, laid out concerns about the possible creation of new
types of infectious rDNA elements and stressed the potential biohazards of
rDNA molecules. The full text of the letter was published in the July 1974 jour-
nal Science and was carefully worded and comprehensible to scientists in the field.
Signers of the letter were representatives of several organizations, including the
Committee on Recombinant DNA Molecules, Assembly of Life Sciences, Na-
tional Research Council, and the National Academy of Sciences.
In the famous "Berg letter," scientists requested that the National Academy
of Sciences give attention to matters relating to rDNA research. In particular, sci-
entists were concerned about elements that could prove biologically hazardous
that is, those capable of exchanging genetic information with other types of
bacteria, some of which were pathogenic to humans. They concluded that scien-
tists have social responsibilities that are a result of their work.
23
Berg and colleagues offered the following proposals: First, until the potential
hazards of such rDNA molecules were better evaluated, scientists throughout the
world should place a moratorium on rDNA research. Second, plans to link frag-
ments of animal DNA to bacterial plasmid DNA should be carefully weighed
since many animal cell DNAs contained sequences common to RNA tumor
viruses. Third, the National Institutes of Health (NIH) should establish an advi-
sory committee charged with overseeing and developing procedures and devising
guidelines for rDNA experiments. Finally, an international meeting of involved
scientists should be convened to review progress and discuss appropriate ways to
deal with rDNA molecules.
24
The NIH took the lead in regulating rDNA research and on October 7, 1974,
established the Recombinant DNA Molecule Program Advisory Committee
(RAC) to study potential rDNA biohazards. After much discussion, the follow-
ing conclusions were reached by members present at the meeting: First, major ef-
forts must be taken to keep decision making within the professional boundaries
of the scientific community; second, little effort should be made to outline the
long-term impacts of rDNA techniques in the industrial sector; and, third, top-level
scientists expressed concern as to who should have monopoly on rDNA research.
Because of these conclusions, a temporary moratorium was initiated.
Asilomar Conference II
On February 24-27, 1975, the International Conference on Recombinant DNA
Molecule Research (Asilomar Conference II) was held at the Asilomar Confer-
ence Center, Pacific Grove, California. The conference was organized for several
reasons: first, to discuss concerns for the possible unfortunate consequences of
indiscriminate application of rDNA technology; second, to review scientific
progress in this area; and third, to propose appropriate ways to deal with poten-
tial rDNA hazards.
Although the primary goal was to devise tight safeguards, there was also
9
THE GENETI CS REVOLUTI ON
concern that if scientists did not set standards for DNA research, it would be
possible for outside groups to intervene. Stanley Cohen of Stanford University
stated that "if the collected wisdom of this group doesn' t result in recommenda-
tions, the recommendations may come from other groups less qualified."
25
One hundred fifty representatives from fifteen countries attended the confer-
ence. Most attendees were generally pleased with the results of the conference,
and members of the press gave the meeting wide and immediate coverage.
Nicholas Wade, a journalist for Science, praised Paul Berg, chair of the Asilomar
II Conference, for his work, saying: "Probably few other people could have asked
for a moratorium, got it to stick worldwide, and then handled the issue with the
openness and disinterest that disarmed resentment and led the world' s scientific
community to a notable and generally harmonious consensus."
26
Attempting to move ahead, conference attendees discussed the possibility of
dispensing with the voluntary moratorium on rDNA experiments. Aware that if
they did not end it, others outside the scientific community might, they voted to
end the voluntary moratorium.
Dr. Robert Sinsheimer, an active participant at the conference, felt that the
U.S. government should stop all genetic research, primarily because of DNA' s
possible evolutionary and social dangers.
27
Sinsheimer argued that a governmen-
tal authority should take responsibility for and restrain this "great and terrible
power."
28
Eventually, Sinsheimer favored a permanent moratorium on DNA ex-
periments. However, no permanent moratorium was ever enacted after the initial,
temporary 1974-75 moratorium.
In addition to lifting the moratorium, conference attendees set up safety
guidelines for future rDNA research.
29
The two guiding principles were: first,
containment of the experiments within specially constructed laboratories, based
on the established practices of scientists working with contagious diseases and tu-
mor viruses; and second, containment of the use of enfeebled vectors (carrier or-
ganisms) for the rDNA molecules. The vectors consisted of mutated strains of
the intestinal bacteria E. coli, which, even if they should escape the experiment
and enter a human intestinal tract, could survive only a short time.
30
Two important items came out of the conference: first, the proposed NIH
Quidelines for Research Involving Recombinant DNA Molecules; and second, the
concepts for physical and biological containment. The NIH later used the
Quidelines as their model for safety in the United States and defined the types of
containment. Physical containment meant limiting the spread of potentially dan-
gerous microorganisms by using specially designed labs, whereas biological con-
tainment involved the use of microorganisms that were attenuated in some way so
they could not live outside lab culture conditions.
31
On April 22, 1975, the Senate Subcommittee on Health, Committee on La-
bor and Public Welfare met to discuss rDNA technology. Senator Edward
Kennedy was chosen to chair the Senate Subcommittee. On May 12-13, the RAC
met to frame guidelines for research with rDNA molecules. An RAC subcom-
mittee meeting was held on July 18-19 to draft provisional guidelines (Woods
Hole Guidelines).
In November 1975 the NIH Advisory Committee asked for public comments
and then published its own proposed safety guidelines. Doubts, fears, and marked
1 D
RECDMBI NI NG DNA MOLECULES
apprehension of scientists and the public were expressed to the committee. Al-
though the guidelines followed the Asilomar principles, they were much stricter
about the levels of safety protection required for particular types of experiments.
During that time a legislative aide to a congressional subcommittee on Health
and the Environment, expecting legislative regulation to prevail, described the
scientists' response to proposed legislation in this way:
Nevertheless, the greatest fear response exhibited by any group came
from the scientists as soon as legislation was proposed. It was particu-
larly frustrating for me to deal with a barrage of protests so fraught
with a nearly total lack of understanding of administrative law, often a
lack of knowledge of the content of particular bills and a failure to dis-
tinguish between the various House and Senate bills. The extent to
which bills were misunderstood, misinterpreted and false conclusions
drawn from them was unbelievable.
. . . The most offensive features of this reaction of scientists was
not their initial ignorance and naivitythat can be forgivenbut their
subsequent refusal to learn. Numerous briefings were held and memo-
randa written to explain in detail how each section of the House bill
should be interpreted, but a significant segment of the scientific estab-
lishment held steadfast to their misconceptions and false conclusions.
This was something worse than hubris and basically unforgivable. . . .
. . . one must conclude that this was purely an instinctive, emo-
tional and defensive response to fear. . . . But fear of what? How could
the mere extension of safety standards by law pose such a threat?
Clearly, if the purpose and content of legislation had been under-
stood in the first place, it wouldn' t have been perceived as a threat at all.
But since it was somehow regarded as control of the content of scientific
research, where scientists were sent to jail for forgetting to plug a pipette,
no wonder such a frozen state of emotional intransigence resulted.
32
Erwin Chargaff, biochemistry professor at Columbia University, expressed
his personal fears in a letter to Science magazine. In the article, Chargaff's main
concern was for future generations and the possible evil results of introducing
new forms of life into the biosphere:
A bizarre problem is posed by recent attempts to make so-called gene-
tic engineering palatable to the public . . . what seems to have been
disregarded completely is that we are dealing here much more with an
ethical problem than with one in public health, and that the principal
question to be answered is whether we have the right to put an addi-
tional fearful load on generations that are not yet born. I use the ad-
jective "additional" in view of the unresolved and equally fearful
problem of the disposal of nuclear waste. Our time is cursed with the
necessity for feeble men, masquerading as experts, to make enor-
mously far-reaching decisions. Is there anything more far-reaching than
the creation of new forms of life? . . . But beyond all this, there arises
1 1
THE GENETI CS REVOLUTI ON
a general problem of the greatest significance, namely, the awesome ir-
reversibility of what is being contemplated. You can stop splitting the
atom; you can stop visiting the moon; you can stop using aerosols; you
may even decide not to kill entire populations by the use of a few
bombs. But you cannot recall a new form of life. . . . An irreversible at-
tack on the biosphere is something so unheard of, so unthinkable to
previous generations, that I could only wish that mine had not been
guilty of it. The hybridization of Prometheus with Herostratus is
bound to give evil results.
33
Chargaff claimed that the ultimate goal of research on gene manipulation was
the correction of genetic abnormalitiesthe replacement of defective genes by
good ones. Chargaff, at the time, had a great mistrust of those he called "biologi-
cal do-gooders," believing that some of the greatest atrocities had been commit-
ted under the pretext of helping suffering humanity.
Academic Involvement
As the war in Southeast Asia began to infiltrate deeply onto college campuses,
scientists and ethicists became deeply involved in the increasing turmoil. At
research institutions of higher learning, such as the Massachusetts Institute of
Technology (MIT), students eagerly helped to prepare technological tools that
would help in the war effort. In campus laboratories all over the United States,
events were taking place that appeared to be almost schizophrenic in nature. On
one hand, rDNA research meant making life easier and more humane for many.
On the other hand, it meant designing means which might effectively provide for
destruction of human life.
Debra Peattie spent a time of the rDNA revolution, 1975-80, as a doctoral
student in the Harvard Biological Laboratories (which she fondly recalls as the
"Bio Labs"). Later, she recalled:
Genetic engineering was an emotionaloften vitriolictopic for sci-
entists in the mid 70's. The summer of 1977 was your typical hot and
muggy Boston summer, whipped to frothing by continuous debates
between individual scientists, groups of scientists, public interest groups,
interested public groups, then Mayor Alfred Vellucci and the Cambridge
City Council.
In the mid 70's, genetic engineering was not viewed with the san-
guine eye it is today. Indeed, there were many people who believed it
quite likely that inserting foreign DNA into bacteria (the "essence" of
genetic engineering if you will) could lead to "killer" bacteria that
could escape from the laboratory and run amuck in the City of Cam-
bridge. How could these killer bacteria escape? One theory postulated
that bacteria would be carried out on the legs of the big South Ameri-
can cockroaches that infested the bio Labs due to the ongoing research
on them there. I kid you not. The more salient question might actually
l 2
RECOMBI NI NG DNA MOLECULES
have been, "Could these bacteria withstand some of the other things
running amuck in the City of Cambridge in the 70's?" But that' s an-
other story. The fact that a child care center operated (and still oper-
ates) behind the Bio Labs raised concerns to a fever pitch: scientists
risking their lives by cloning foreign genes into bacteria were one
thing, but innocent children threatened by the recombinant bacteria
wafting out of air vents or windows was another thing. So much for
thesis work being boring, as I used to tell my parents on the phone.
I was working in the laboratory of Walter Gilbert, a man who was
racing to clone the human insulin gene and who was in the midst of
performing his Nobel Prize winning research, so life was far from dull
for those of us in the lab at the time. Gilbert' s scientific stature and pro-
genetic engineering stance turned the summer of 1977 into an ongoing
exchange between the lab and the news media, the public, other labs,
other universities, other scientists, you name it. Incoming telephone
calls about genetic engineering got so numerous that some of us just
took the lab phone off the hook in order to get our work done; others
took to answering the phone with a terse "No comment." A couple of
us from the lab lugged a six-foot-tall DNA molecule by car down to the
then-bare fields of Kendall square for a Harvard-MIT "teach-in" about
recombinant DNA and genetic engineering for the public that summer,
and others of us went before the Cambridge City Council to testify at a
hearing about the safety of the revolutionary new technology. After re-
ceiving obscene telephone calls at home due to my defense of genetic
engineering in front of the Cambridge City Council, I emulated our lab
practice and took the phone off the hook, too.
The Cambridge City Council decided it needed time to digest the
information it had gathered about genetic engineering, and the City de-
clared a moratorium on recombinant DNA research. The Department
of Biochemistry and Molecular Biology lost a newly hired professor to
Cal Tech because he would have been unable to perform his research in
moratorium-bound Cambridge. Students and post-docs were thrown
into a frenzy because they suddenly could not do the experiments they
needed for their theses and research fellowships. Luckily, Harvard
Medical School was in Boston and unfettered by the moratorium, so
work could continue therealbeit on tenterhooks while the public
and scientific community were still fractured by debate.
So what happened to the controversy? The moratorium eventually
ended, the City of Cambridge was threatened more by its everyday ec-
centricities rather than by killer recombinant bacteria, the Cal Tech
professor moved to Harvard as he had originally intended and the prac-
tice of gene cloning evolved from a closely monitored novelty to the
immensely powerful science that produced Humulin, the genetically
engineered insulin that Eli Lilly licensed from Genentech and that got
me started on all of this in the first place. Funny, it all seems like just
yesterday instead of eighteen years ago. Forget those killer bacteria
that' s the really scary part!
34
l 3
THE GENETI CS REVOLUTI ON
NIH Guidelines
An enormous amount of time, thought, and labor went into producing the guide-
lines for rDNA technology. In November 1975 the NIH Advisory Committee
published its own proposed NIH Quidelines. Designed primarily to diffuse the
rDNA controversy, the Quidelines represented a negotiated settlement. At its De-
cember 4-5, 1975, meeting the RAC adopted proposed guidelines for rDNA re-
search that were carried out with NIH funding. The meeting included many
noted scientific and public representatives, and as a result many useful comments
and suggestions were received.
In February 1976, Maxine Singer made a presentation before the NIH Direc-
tor' s Advisory Committee (DAC), citing four principles:
35
First, in light of current information, certain experiments may be judged to
present sufficiently serious potential hazards so that they should not be at-
tempted at this time;
Second, the group of experiments that pose either lesser or no potential hazards
could be performed provided (a) the information to be obtained or the practical
benefits anticipated could not be obtained by conventional methods, and (b) ap-
propriate safeguards for containment are incorporated into the design;
Third, the more potentially hazardous the experiment, the more stringent
should be the safeguards against escape of the agents;
Finally, that there should be an annual review of the Quidelines.
On June 9-12, 1976, the Ten Miles International Symposium on Recombi-
nant DNA Molecules: Impact on Science and Society meeting was held at the
Massachusetts Institute of Technology in Cambridge, Massachusetts. Essentially,
this was an RAC working group on safer hosts and vectors. Shortly thereafter, on
June 23, 1976, the RAC issued the Quidelines for rDNA research. The Quidelines
required rDNA research proposals to first be reviewed by the home institution' s
biosafety committee (IBC) and then by the RAC. It was determined that because
of federal regulations on research involving human subjects, rDNA research must
be reviewed by the local IBC.
The Quidelines applied to all federally funded institutions performing rDNA
research, regardless of the source of funding for the specific project or where the
research took place. The Quidelines specified that there must be levels of physical
and biological containment which were dependent on the kinds of experiments
conducted. The four levels of physical containment were PI, P2, P3, and P4.
PI corresponded to microbiology diagnostic laboratories in all hospitals; P2
referred to biological safety cabinets used in most operations; P3 designated in-
ward air flow in all laboratories, much like a giant hood, as well as overall special
practices for each laboratory; and P4 designated that all experiments must be
confined to air-tight biological safety cabinets and that scientists must perform
their work through glove ports.
In addition, the Quidelines discussed roles and responsibilities of all scientists
conducting rDNA research, his or her university affiliation, members of the uni-
1 4
RECOMBI NI NG DNA MOLECULES
versity's biosafety committee, and the NIH. After their promulgation in 1976,
the NIH Quidelines were accepted by other federal agencies including the Na-
tional Science Foundation (NSF) and the U.S. Department of Agriculture.
Some of these views found support in Washington, DC. In July 1976 Sena-
tors Jacob Javits and Edward Kennedy wrote to President Gerald Ford, urging
that "every possible measure be explored for assuring that the NIH Quidelines
were adhered to in all sectors of the research community."
36
Senators Javits and Kennedy also wrote that they were "gravely concerned
that these relatively stringent (NIH) guidelines may not be implemented in all
sectors of the domestic and international research communities and that the
public will therefore be subjected to undue risk. . . . We urge you to implement
these [NIH] Quidelines immediately whenever possible by executive directive
and/or rule making, and to explore every possible mechanism to assure com-
pliance."
37
Earlier, Senator Kennedy had been critical of scientists who made public pol-
icy in private. Favoring more public participation in science, he drafted a bill that
would have established an independent national regulatory commission specifi-
cally for rDNA research. Composed primarily of nonscientists, the commission
would control all rDNA research (except that local communities could set more
severe restrictions, or ban the research altogether).
Later, at a risk assessment workshop in Falmouth, Massachusetts, on June
20-21, 1977, it was concluded that Escherichia coli K-12 was a harmless organism
and could not be converted into a pathogen by insertion of rDNA. President
Gerald Ford created the Federal Interagency Advisory Committee on Recombi-
nant DNA Research and in 1977, the committee recommended new legislature to
extend the NIH Quidelines to private industry.
Based on approximately 170 responses from persons who had expressed con-
cerns over rDNA, revision of the NIH Quidelines was issued in December 1978.
The revised Quidelines contained many steps and some major changes. First, ex-
periments in general were assigned lower levels of required containment. Second,
certain classes of experiments deemed of the lowest potential hazard were ex-
empted entirely from the guidelines. Third, increased representation was man-
dated on local institutional biosafety committees that monitored rDNA research
at individual institutions and on the RAC. Finally, procedures were built into the
guidelines for changing them in the future. This was considered a major change
where any person wishing to suggest a revision of the Quidelines could submit
them to NIH. The Quidelines were published by the Federal Register at least thirty
days before a regular meeting of the RAC, for public comment. Members of the
public were encouraged to speak on the subject.
38
In 1981 the NIH took the first steps toward removing mandatory controls on
the conduct of rDNA research. Meeting in Bethesda, Maryland, the RAC set up
a subcommittee to look into the future of the Quidelines and to discuss whether
then-current Quidelines, which all federally sponsored scientists had to observe,
should be turned into a voluntary code of practice.
The committee considered two proposals, both of which would relax current
mandatory guidelines. The first proposal, offered by Dr. Allan Campbell of Stan-
ford University and Dr. David Baltimore of M.I.T., suggested that the NIH
i 5
THE GENETI CS REVOLUTI ON
Quidelines should be voluntary, thus eliminating the formal need for review by bod-
ies such as local institutional biosafety committees. Baltimore suggested that the
RAC continue to monitor rDNA research, to make decisions about experiments
that would present certain dangers, and to help evaluate significant ethical issues.
In addition, Campbell and Baltimore suggested that specifics should be re-
viewed by the NIH director in order to monitor large-scale experiments that
might have unsuspected results. They also suggested that there should be major
reductions in the containment levels recommended for various types of rDNA
experiments. However, other members, particularly those from the public inter-
est community, were cautiously opposed to reducing the containment conditions
too quickly.
The other proposal was a mandatory plan that loosened present experimen-
tal restrictions, but not to the extent of the RAC' s September proposal. The pro-
posal was offered by Susan Gottesman, a senior investigator in molecular biology
at the National Cancer Institute and a former RAC member. Her proposal re-
tained Institutional Biosafety Committees, which the RAC proposal eliminated.
However, the proposal by Gottesman did not lower containment levels as much
as the RAC proposal. Gottesman' s proposal passed sixteen to five.
Elena Nightingale of the Institute of Medicine stated: "We should keep in
mind that the probability of something going wrong is small, but . . . [if some-
thing goes wrong] the consequences are large. A powerful technology has power-
ful consequences."
39
However, many committee members were uncomfortable with the prospect
that the public might react negatively if the NIH Quidelines were made voluntary.
Urging a careful relaxation of the rules, William N. Lipscomb, chair of Harvard' s
Biosafety Committee, in a letter to the committee warned that public concern
and subsequent actions "should not be underestimated." Some committee mem-
bers thought it possible that various kinds of state and local regulations might
spring up across the country if the NIH abandoned the mandatory guidelines.
Baltimore argued that the RAC proposal "tries to reflect the judgment of a
vast majority of scientists who believe that rDNA research is no more hazardous
than the mainstream of research. Those who do not agree with me represent, at
best, a small fraction of the scientific community."
40
Given the commendable track record of most scientists, committee members
agreed that the risks of hazards in rDNA research were small. As a result, con-
troversy over rDNA research intensified and charges of conflict of interest were
fired against Baltimore. At the time, he served as a board member and chair of a
scientific advisory committee at a biotechnology company called Collaborative
Research while at the same time he retained his faculty post at Harvard.
The NIH committee chose to keep the rules mandatory for two principal rea-
sons. First, some members were clearly worried about public backlash and the
possibility that the removal of federal regulation would invite local and state leg-
islators to enact their own laws to restrict rDNA research. Second, some mem-
bers had lingering concerns about the safety of some experiments regulated by
guidelines.
Several RAC members pointed out that there was still considerable public
fear about rDNA research and suggested that rDNA research be regulated in a
l 6
RECDMBI NI NG DNA MOLECULES
responsible manner. In 1981, the RAC recommended that virtually all the re-
maining "requirements" be converted to "recommendations," since federal con-
trols no longer seemed necessary. Acting on behalf of, and with the endorsement
of, the Assembly of Life Sciences of the National Research Council, the RAC
proposed a number of recommendations.
The first recommendation involved two types of DNA recombination. Type 1
described construction of new, autonomously replicating bacterial plasmids that
might result in the introduction of genetic determinants for antibiotic resis-
tance or bacterial toxin formation into bacterial strains that did not at the pres-
ent time carry such determinants; or construction of new bacterial plasmids
containing combinations of resistance to clinically useful antibiotics unless plas-
mids containing such combinations of antibiotic resistance determinants already
existed in nature.
Type 2 discussed linkage of all or segments of the DNAs from oncogenic or
other animal viruses to autonomously replicating DNA elements such as bacter-
ial plasmids or other viral DNAs. They reasoned that rDNA molecules might be
more easily disseminated to bacterial populations in humans and other species,
and thus possibly increase the incidence of cancer or other diseases.
The second recommendation discussed plans to link fragments of animal
DNAs to bacterial plasmid DNA or bacteriophage DNA. It expressed concern
that this should be carefully weighed in light of the fact that many types of ani-
mal cell DNAs contained sequences common to RNA tumor viruses. Since join-
ing of any foreign DNA to a DNA replication system created new recombinant
DNA molecules whose biological properties could not be predicted with cer-
tainty, the committee reasoned that such experiments should not be taken lightly.
The committee' s third recommendation was that the director of the National
Institutes of Health be requested to give immediate consideration to establishing
an advisory committee charged with (a) overseeing an experimental program to
evaluate the potential biological and ecological hazards of the above types of re-
combinant DNA molecules, (b) developing procedures that would minimize the
spread of such molecules within human and other populations and, (c) devising
guidelines to be followed by investigators working with potentially hazardous re-
combinant DNA molecules. It was suggested that these standards would be en-
forced through the NIH and other government agencies that disburse government
research grants.
The fourth recommendation advocated an international meeting of involved
scientists from all over the world to be convened early in the coming year to re-
view scientific progress in this area and to further discuss appropriate ways to deal
with the potential biohazards of rDNA molecules and recombination techniques.
In February 1982 a National Institutes of Health Advisory Panel voted to re-
lax somewhat the regulations that governed federally funded rDNA research. At
the same time they approved keeping the Quidelines compulsory and in so doing,
the RAC continued steering a conservative course on rDNA research. The panel
strongly rejected another proposal that would have made the Quidelines com-
pletely voluntary because most committee members were not ready to forgo all
the restrictions and oversight that the NIH had exercised over rDNA research
since 1976.
l 7
THE GENETI CS REVOLUTI ON
Not surprisingly, the United States was not the only country that had trouble
in setting up rDNA research guidelines. In 1990 Germany passed a gene technology
law that was very similar to the NIH' s safety Quidelines outlined at the Asilomar
Conference. However, German scientists were very unhappy with the strictness
and enforcement policies of the new law. In addition, the German people were
very fearful of the words "genetic engineering" because they feared that the Ger-
man people might be used for eugenic purposes as proposed during Hitler' s
regime or that German scientists might deceive them about the safety of the
r DNA experiments.
l B
2
SPLI CI NG LI FE
Technological Revolution or Pandora's Box?
At this point in the development of genetic engineering no rea-
sons have been found for abandoning the entire enterprise
indeed, it would probably be naive to assume that it could be.
Given the great scientific, medical, and commercial interest in
this technology, it is doubtful that efforts to foreclose important
lines of investigation would succeed. If, for example, the United
States were to attempt such a step, researchers and investment
capital would probably shift to other countries where such pro-
hibitions did not exist. To expect humanity to t urn its back on
what may be one of the greatest technological revolutions may it-
self betray a failure to recognize the limits of individual and so-
cial restraint.
Morris B. Abram, chair of the President's
Commission for the Study of Ethical Problems
in Medicine and Biomedical Research
Current concerns about biological, chemical, and nuclear-weapons terrorism
remind us of how well-intentioned scientific advances, such as recombinant
DNA (rDNA) technology, provide human beings with vast powers that may
endanger our fundamental social and political values. Yet, the spector of
such power has haunted the development of r DNA technology since its begin-
nings in the 1970s. Whereas some claim the scientific development of r DNA
technology to be a huge success, others fear it may have opened a Pandora' s
box.
THE GENETI CS REVOLUTI ON
Social and Political Actions
Initial public debate over the rDNA issue created a storm of social and political
action, with government agencies scrambling to acquire new regulatory territory.
Overall, there was an increased public mistrust of rDNA technology, and the fun-
damental question raised was, what shall be regulated and by whom? because the
NIH Quidelines didn' t apply to private individuals there was fear that profit might
overshadow scientific integrity. As a result of the general mistrust about rDNA
technology, rapid commercialization became a real possibility.
Erwin Chargaff once again expressed concerns about rDNA technology, stat-
ing that he had five main objections to the new technology. First, he objected to
using E. coli as the host in rDNA experiments, believing that a more extensive
search would have resulted in a better choice of a host; second, he felt that soci-
ety would not be safe from anything that needed to be contained; third, he felt
that too much money would be wasted on rDNA research and that other kinds of
research would be ignored because of it; fourth, he felt that industrial research
and production would be dangerous because they were outside government rela-
tions; and, finally, he believed that the uncertainty of rDNA research might result
in one mistake changing the biosphere irreversibly.
1
Scientists became engaged in political debate over the new technology, and
legislative and administrative regulation seemed a compelling necessity. However,
from the scientists' viewpoint, as well as the public interest, legislative regulation
would be the worst thing that could happen, largely because enactment of legisla-
tion would have been a triumph for the leftist political ideology. However, some
legislators and their aides saw it in a different light.
2
During 1977 and the beginning of 1978 many scientists agreed that the risks of
rDNA research were, at worst, more minimal than they had previously estimated
perhaps even nonexistent. This consensus grew after S. Chang and S. N Cohen
wrote a scientific paper that announced that rDNA was also produced in nature.
3
Chang and Cohen' s paper was considered the scientific turning point in the debate
over whether rDNA research should be stopped because it demonstrated that
rDNA production was not an unprecedented tampering with the balance of nature.
As a result, Chang and Cohen, as well as other scientists, gained the attention
of several senators including senators Edward Kennedy and Adlai Stevenson. In
September 1977 Stevenson called on the Senate to put off legislation on rDNA
technology and Senator Kennedy withdrew support for his sponsored Senate
bill, joining with those who viewed the hazards of rDNA as questionable.
Interest/Action Groups
During the middle and late 1970s interest and action groups met to discuss the
rDNA issue. One of the leading centers concerned with the rDNA technology is-
sue was the Hastings Center, located in Hastings-on-Hudson, New York. The
Hastings Center enjoyed a sterling reputation and played a key role in interna-
tional risk assessments, participating in some Gordon Conferences. Started in
1969 by Daniel Callahan, the Hastings Center was originally designed to sponsor
2 D
SPLI CI NG LIFE
workshops, publish teaching materials, and promote interdisciplinary research
groups. The center also issued a bimonthly journal that contained essays on legal
and ethical issues in science and medicine.
Other interest/action groups entered the picture at about this same time, includ-
ing the Federation of American Scientists (FAS), the oldest, largest, and strongest of
the politically moderate groups. The FAS believed that it was their responsibility to
inform the public on matters dealing with the technical and scientific importance
of rDNA research. Also appearing on the scene was the Society for Social Respon-
sibility in Science (SSRS), first conceived in 1949 and designed to push for "con-
structive alternatives to militarism." The SSRS, like the FAS, stressed the need to
create an informed public opinion on rDNA technology issues.
In 1976 Jeremy Rifkin, president of the Foundation on Emerging Technologies
(an organization based in Washington, DC. ) made public his organization's oppo-
sition to rDNA technology. Considered by many as one of the most prominent op-
ponents of rDNA technology, Rifkin sponsored numerous lawsuits against genetic
engineering experiments and organized public protests against biotechnology.
Rifkin had written several books including Declaration of a Heretic and Algeny,
in which he depicted genetic engineering as having the potential to redesign the hu-
man race. Rifkin worried that the future of mankind might be redesigned to change
racial or socially undesirable traits, considered by some as a form of eugenics.
4
Worried that genetic information might be widely used to discriminate against in-
dividuals attempting to obtain employment, education, or insurance, Rifkin pre-
dicted a genetic rights movement as potent and as powerful as the civil rights
movement of the 1960's.
5
'
6
Rifkin introduced a bill before the Government Operations Committee that
was designed to regulate the collection, maintenance, use, and dissemination of
genetic information gathered from individuals by the federal government and its
contractors and grantees. The bill prohibited agencies from releasing genetic in-
formation without the individual's written consent, except in the case of a med-
ical emergency or a criminal investigation where probable cause of reasonable
suspicion had been shown. In addition, the bill gave individuals the right to file a
lawsuit or an injunction against an agency that had released, or was intending to
release, information without permission. It also provided criminal penalties for
unauthorized release.
7
Rifkin requested a voluntary moratorium and public debate on all human gene
therapy research, and he asked that all gene therapy experiments cease until the NIH
was able to set up a committee to evaluate the ethical and social issues of human
gene research. Rifkin filed a lawsuit in federal court to stop gene therapy experi-
ments on the grounds that the NIH' s review of the experiments was flawed. He
charged the NIH' s RAC of ignoring the ethical issues of human gene therapy, refer-
ring to them as an elite group of NIH scientists with handpicked ethical consultants.
Rifkin formed his own committee, the Human Eugenics Advisory Commit-
tee, composed of people in the fields of civil liberties, the rights of disabled work-
ers, and insurance and consumer rights. The newly-formed committee provided
advice on the ethical, social, economic, and eugenic implications and impacts of
human genetic therapy.
8
However, some RAC members felt that Rifkin was more
interested in setting up a public debate than in stopping gene research. As a result,
2 l
THE GENETI CS REVOLUTI ON
RAC members voted to "respectfully decline" Rifkin's proposal for a public de-
bate. His request for a moratorium was denied and no national debate was held.
9
In March 1977 the National Academy of Sciences organized an Academy Fo-
rum on rDNA Research. The Hastings Center, led by Daniel Callahan and col-
leagues, was instrumental in getting scientists, philosophers, and legal experts
together to discuss rDNA and its implications. In the spring of 1978, Sydney
Brenner, a participant at the Asilomar Conferences and a distinguished scientist
at the Medical Research Council' s Laboratory of Molecular Biology in Cam-
bridge, England, produced a substantive paper for the Genetic Manipulation Ad-
visory Group (GMAG), the British counterpart to RAC. In the paper, Brenner
suggested a generalized framework to estimate the potential biohazards of differ-
ent classes of experiments.
10
In the late 1970s Nobel laureate James D Watson came to the forefront of the
rDNA debate. Speaking in opposition to radical groups wanting to shut down
rDNA research, he wrote in the Washington Post: "Such groups thrive on bad
news, and the more the public worries about the environment, the more likely we
are to keep providing them with the funds that they need to keep their organiza-
tions going. So if they do not watch themselves, they will always opt for the worst
possible scenario."
11
In January 1979 Health, Education, and Welfare Secretary Joseph Califano of
the Recombinant DNA Advisory Board invited members from several radical or-
ganizations and environmental groups to participate in discussions. Only the
most activist environmental groups expressed opposition to rDNA research, and
even they were under severe internal criticism from scientists who were promi-
nent trustees of groups such as Friends of the Earth and the Natural Resources
Defense Council.
The 95th Congress and Recombinant DNA Technology
In the late 1970s the U.S. government had become moderately concerned over
the possible risks involved in rDNA technology. As a result, during most of
1977 there was a scramble among government agencies to acquire new regulatory
territory. The Ninety-fifth Congress, which lasted through all of 1977 to January
of 1978, saw fifteen different bills on rDNA technology introduced. In general,
there was substantial disagreement among the legislators and a lack of interest in
controlling rDNA research. Subsequently, none of the bills ever reached the floor
of the full House or Senate.
Patenting Life Forms
Opponent s of rDNA technology expressed substantial fear that profit from
rDNA research and technology might supersede scientific integrity. The fear was
enhanced when patents were issued by the U.S. Patent Office in June 1980 to
Dr. Ananda Chakrabarty for a specially created Pseudomonas aeruginosa bacterium
that could break down oil slicks, and to Cohen and Boyer in December 1980 to
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cover the basic process involved in generating rDNA molecules.
12
At the time,
the idea that a newly created life form could be patented was unique.
History recorded the landmark 1980 Supreme Court case of Diamond vs.
Chakrabarty as the pivotal case of biotechnology.
13
What frightened most people
at the time was the process of recombining DNA molecules and the capability to
alter genetic properties of organisms by design.
14
There was also the fear that
competition in patenting life forms might lead to a stifling of communication be-
tween scientists.
Churches
1
Concerns
During this same time, ethical and moral issues concerning rDNA technology
were discussed in many churches throughout the United States and the world. In
the United States the National Council of Churches commissioned a Task Force
on Human Life and the New Genetics, which concluded:
Possibilities such as cloning, mass genetic screening, and gene therapy
challenge our understanding of the nature of personal identity, the
meaning of human community, the inviolability of the body, the struc-
ture of human parenthood, and the limits on human intervention into
natural processes. There is reason to ask of any specific genetic practice
whether or not it is a rash act with unpredictable consequences. There
is reason to ask also, as in any human exercise of power, whether or not
it is an instrument for a strong elite to impose its prejudices on the less
powerful. Such questions may lead to an ethical judgment that some
genetic possibilities should not be exploited, now or ever. But that
judgment, if made, is a specific judgment, not a universal rejection of
genetic activity. Theologically understood, God may work as truly
through intentionally human genetic acts as through the human unin-
tended genetic processes that have made humanity genetically what it is
now. The task force's report offered a sense of balance, neither con-
demning the new technology nor applauding it. The report was not de-
signed to set forth any policy but was prepared to help people think for
themselves and find their own convictions.
15
On July 20, 1980, the following letter was sent to U.S. president Jimmy Carter
by the General Secretariats of the three main religious councils in America: Dr.
Claire Randall, General Secretary of the National Council of Churches; Rabbi
Bernard Mandelbaum, General Secretary of the Synagogue Council of America;
and Bishop Thomas Kelly, General Secretary of the U.S. Catholic Conference.
Dear President Carter:
We are rapidly moving into a new era of fundamental danger trig-
gered by the rapid growth of genetic engineering. Albeit, there may be
opportunity for doing good; the very term suggests the danger. Who
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THE GENETI CS REVDLUTI DN
shall determine how human good is best served when new life forms
are being engineered? Who shall control genetic experimentation and
its results which could have untold implications for human survival?
Who will benefit and who will bear any adverse consequences, directly
or indirectly?
These are not ordinary questions. These are moral, ethical, and re-
ligious questions. They deal with the fundamental nature of human
life and the dignity and worth of the individual human being.
With the Supreme Court decision allowing patents on new forms
of lifea purpose that could not have been imagined when patent
laws were writtenit is obvious that these laws must be reexamined.
But the issue goes far beyond patents.
New life forms may have dramatic potential for improving human
life, whether by curing diseases, correcting genetic deficiencies or swal-
lowing oil slicks. They may also, however, have unforeseen ramifica-
tions, and at this time the cure may be worse than the original problem.
New chemicals that ultimately prove to be lethal may be tightly con-
trolled or banned, but we may not be able to "recall" a new life form.
For unlike DDT or DES, both of which were in wide use before their
tragic side effects were discovered, life forms reproduce and grow on
their own and thus would be infinitely harder to contain.
Control of such life forms by an individual or group poses a po-
tential threat to all of humanity. History has shown us that there will al-
ways be those who believe it is appropriate to "correct" our mental and
social structures by genetic means, so as to fit their vision of humanity.
This becomes more dangerous when the basic tools to do so are finally
at hand. Those who would play God will be tempted as never before.
We also know from experience that it would be naive and unfair to
ask private corporations to suddenly abandon the profit motive when
it comes to genetic engineering. Private corporations develop and sell
new products to make money, whether those products are automobiles
or new forms of life. Yet when the products are new life forms, with all
the risks entailed, shouldn' t there be broader criteria than profit for de-
termining their use and distribution? Given all the responsibility to
God and to our fellow human beings, do we have the right to let exper-
imentation and ownership of new life forms move ahead without pub-
lic regulation?
These issues must be explored, and they must be explored now. It
is not enough for the commercial, scientific, or medical communities
alone to examine them; they must be examined by individuals and
groups who represent the broader public interest. In the long-term in-
terest of all humanity, our government must launch a thorough exam-
ination of the entire spectrum of issues involved in genetic engineering
to determine before it is too late what oversight and controls are nec-
essary.
We believe, after careful investigation that no government agency
or committee is currently exercising adequate oversight or control,
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not addressing the fundamental ethical questions in a major way.
Therefore, we intend to request that President Carter provide a way
for representatives of a broad spectrum of our society to consider
these matters and advise the government on its necessary role.
We also intend to ask the appropriate Congressional Committees
to begin immediately a process of revising our patent laws looking to
revisions that are necessary to deal with the new questions related to
patenting life forms. In addition, we will ask our government to col-
laborate with other governments with the appropriate international
bodies, such as the UN. , to evolve international guidelines related to
genetic engineering.
Finally, we pledge our own efforts to examine the religious and
ethical issues involved in genetic engineering. The religious commu-
nity must and will address these fundamental questions in a more ur-
gent and organized way.
16
President Carter's Commission
Aware of the potential dangers of rDNA technology and at the prompting of var-
ious church and synagogue councils, President Jimmy Carter set up the Commis-
sion for the Study of Ethical Problems in Medicine and Biomedical and Behavioral
Research. The commission later issued its published report, Splicing Life: The So-
cial and Ethical Issues of Qenetic Engineering with Human Beings.
In its report, the Carter Commission strongly defended the continuation of
rDNA research and suggested that the RAC broaden its view and include the eth-
ical and social implications of gene therapy. In effect, the commission' s report de-
nied the claim that rDNA was immoral because it had the potential to grant
humans God-like powers, but rather concluded that rDNA technology was like
any number of creative activities of God. Ultimately, the use of the new technol-
ogy was not claimed to be wrong as such but wrong because of its potential con-
sequences.
17
The Carter Commission examined many potentially dangerous consequences
of rDNA technology, including whether rDNA would interfere harmfully with
evolution, destroy parents' rights and sense of responsibility to their children,
change peoples' sense of being human beings and the way they thought of them-
selves, and promote misuses between commercial interests and academic research
projects.
In considering the risk of destroying parental responsibility, the Carter Com-
mission noted that if rDNA technology made use of reproductive techniques such
as in vitro fertilization and artificial insemination, strains on traditional views of
family and kinship would be exacerbated. In discussing potential effects of rDNA
technology on personal identity, the commission reported that the "manipula-
tion of genes that contribute significantly to personality or intelligenceif it ever
becomes possiblecould have considerable impact on the way people think of
themselves. The Commission is intent on using a utilitarian calculus of benefits
and risks."
18
2 5
THE GENETI CS REVDLUTI DN
In its final arguments on social and ethical issues, the commission concluded
that genetic engineering and research should not be halted:
At this point in the development of genetic engineering no reasons
have been found for abandoning the entire enterpriseindeed, it
would probably be naive to assume that it could be. Given the great
scientific, medical, and commercial interest in this technology, it is
doubtful that efforts to foreclose important lines of investigation
would succeed. If, for example, the United States were to attempt such
a step, researchers and investment capital would probably shift to
other countries where such prohibitions did not exist. To expect hu-
manity to t urn its back on what may be one of the greatest technolog-
ical revolutions may itself betray a failure to recognize the limits of
individual and social restraint.
19
On November 16, 1982, Morris B. Abram, Chair of the President's Com-
mission for the Study of Ethical Problems in Medicine and Biomedical Research,
wrote the following letter to President Ronald Reagan:
Dear Mr. President:
On behalf of the President's Commission for the Study of Ethical
Problems in Medicine and Biomedical Research, I am pleased to trans-
mit Splicing Life, our report on the social and ethical issues of genetic
engineering with human beings. This study, which was not within the
Commission' s legislative mandate, was prompted by a letter to your
predecessor in July, 1980 from Jewish, Catholic, and Protestant church
associations. We embarked upon it, pursuant to 1802(a)(2) of our
statute, at the urging of the President's Science Advisor.
Some people have suggested that developing the capability to
splice human genes opens a Pandora' s box, releasing mischief and
harm far greater than the benefits for biomedical science. The Com-
mission has not found this to be the case. The laboratory risks in this
field have received careful attention from the scientific community and
governmental bodies. The therapeutic applications now being planned
are analogous to other forms of novel therapy and can be judged by
general ethical standards and procedures, informed by an awareness of
the particular risks and benefits that accompany each attempt at gene
splicing.
Other, still hypothetical uses of gene splicing in human beings
hold the potential for great benefit, such as heretofore impossible
forms of treatment, as well as raising fundamental new ethical con-
cerns. The Commission believes that it would be wise to have engaged
in careful prior thought about steps such as treatments that can lead to
heritable changes in human beings or those intended to enhance hu-
man abilities rather than simply correct deficiencies caused by well-
defined genetic disorders. In light of a detailed analysis of the ethical
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and social issues of this subjectissues beyond the purview of exist-
ing mechanisms for Federal oversightthe Commission suggests sev-
eral possible means, in the private as well as the public sector, through
which these important matters can receive the necessary advance con-
sideration.
The Commission is pleased to have had an opportunity to partici-
pate in the consideration of this issue of public concern and impor-
tance.
Respectfully,
Morris B. Abram, Chairman
20
Continuing Debate
Originally, three main arguments were proposed and publicly debated with regard to
rDNA technology. The first argument, titled the "free inquiry principle," stated that
rDNA research should not be controlled or restrictedthat scientists should have
full and unqualified freedom to conduct rDNA research as they saw fit.
The second argument, termed the "doomsday scenario," stated that there
should be a total ban on rDNA research and it should be halted. Opponents of
rDNA technology believed that even with low-risk DNA experimentation there
was potential to produce long-term dangers and consequences or even eliminate
our entire species and society.
The third argument advocated a moratorium. New organisms of any kind or
for any purpose would not be created, even if there were no dangerous side effects.
In defending rDNA technology, scientists gave three reasons why they be-
lieved that the risks of rDNA technology were low. First, genetic engineering
techniques allowed the DNA being inserted to be confined precisely to the gene(s)
of interest and their controlling elements. Because the chemical sequence of the
DNA could be determined before insertion, undesirable traits would not be in-
troduced.
Second, virulence in microorganisms requires the operation of many genes.
The insertion of a limited number of defined genes would be highly unlikely to
cause such a major change to the host organism and the likelihood that a non-
pathogenic organism would be converted to a pathogenic one.
Third, evolution itself results from the selection of successful mutations that
occur randomly in nature. The new rDNA techniques simply increase the rate
and precision of such changes, with minimal risk. Proponents of rDNA technol-
ogy, however, stressed strict care and monitoring each time a new product was re-
leased into the environment or a new procedure was conducted.
21
Rifkin on the March
In June 1983 activist Jeremy Rifkin and his organization, The Foundation on Eco-
nomic Trends, issued a resolution on theological issues in genetic engineering
2 7
THE GENETI CS REVDLUTI DN
research. Signed by sixty-three religious leaders and scientists, the basic premise
of the resolution was that efforts to engineer genetic traits into the germ line of
the human species should not be attempted. Rifkin and his supporters felt that
there would be an ecological price to pay if genes were eliminated from the gene
pool. Signers of the resolution said they were concerned about the price that
would be paid in attempting to perfect the human species.
22
Rifkin continued his attempt to stop rDNA experiments and in 1984 he suc-
ceeded in temporarily stopping rDNA experiments on potato plants in Califor-
nia. The potatoes were to be sprayed with a bacterium, Pseudomonas syringae,
which had been genetically altered to protect the plants from frost. Rifkin and his
followers claimed that the "altered bacteria" would cause some plants and insects
to grow unpredictably at the expense of others.
Launching a lawsuit, Rifkin claimed that the RAC did not have unbiased per-
sonnel because all members were molecular biologists except for one terrestrial bi-
ologist who had joined the RAC after it had already approved field tests. The lawsuit
ended in Rifkin's favor when Judge John Sirica ordered the spraying stopped.
Other Groups Surface
In 1984 the RAC created a new group called the Working Group on Human Gene
Therapy, later called the Human Gene Therapy Subcommittee (HGTS). The pur-
pose of the organization was to review gene therapy proposals. The first act of the
Working Group was to produce the document Points to Consider for Protocols for
the Transfer of Recombinant DNA into the Qenome of Human Subjects, a guide for
those applying for RAC approval of gene therapy protocols. The group received
public comments and by late 1985 the RAC subcommittee had revised the Points
to Consider document and was ready to revise gene therapy protocols.
The Sharpies vs. Davis Debate
In 1987 Science printed a debate between Frances E. Sharpies and Bernard D
Davis, members of the RAC. The debate was over the safety of using genetically
engineered organisms in the environment. In the debate, Sharpies advocated regu-
lation of genetically engineered products and stressed evaluation and regulations
of both genetic and ecological properties. Sharpies argued that environmental
concerns over genetically engineered products were different from the laboratory
uses of these products. In making her point, Sharpies stressed that it was neces-
sary to take into consideration all of the human and nonhuman species in an eco-
logical setting that might be exposed to the released organism.
In the Science article, Sharpies pointed out that adding new organisms could
influence the structure and also the energy of an ecological community. She
pointed out that the degree of control was far different between experiments con-
tained in a laboratory and those that involved the release of organisms in the field.
Sharpies also emphasized that differences in scale were a factor to consider with
"new" releases into the environment. Field testing, she said, was on a considerably
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smaller scale than that on which products are marketed and made available for
public use. Sharpies advocated environmental regulations to safeguard against
possible environmental problems.
23
Davis, on the other hand, felt that environmental regulations, set by the En-
vironmental Protection Agency (EPA), were "too restrictive and elaborate." He
also felt that environmental activists were too influential in setting the agenda of
genetic field testing, and he advocated that the scientific community help society
distinguish reasonable probabilities from remote fantasies.
24
Gene Therapy Protocols
On January 19, 1989, the U.S. government signed off on the first approved intro-
duction of a foreign gene into humansa research protocol that had undergone
exhaustive review.
25
An experiment to insert genes into humans prompted Jeremy
Rifkin and the Foundation on Economic Trends to initiate a lawsuit. As a result,
under the terms of the settlement, the NIH agreed to alter the charter of the RAC
to make the approval process for gene transfer protocols more openly explicit.
26
RAC approval was deemed necessary for gene therapy protocols supported
by federal funds. In addition, approval by the U.S. Food and Drug Administra-
tion (FDA) was also necessary. It was further decided that approval by the RAC
and the FDA could be obtained simultaneously or sequentially, in either order.
The FDA focused on the safety of the manufacturing process, the safety and effi-
cacy of the genetically altered products, and on control of the final product. In
1991, the FDA published its revised Points to Consider in Human Somatic Cell Ther-
apy and Qene Therapy. It revised the document again in 1993.
In December 1992 Dr. Bernadine Healy, then Director of NIH, approved a
"compassionate use exemption" from the regular review process, allowing a crit-
ically ill patient to receive gene therapy. The compassionate use exemption, rather
than the regular approval process, proved to be very controversial and, as a result,
additional meetings were required to create RAC procedures for dealing with ex-
pedited review of single patient protocols.
President Clinton's National Bioethics Advisory Commission
In October 1995 President Clinton issued an executive order that established the
National Bioethics Advisory Commission (NBAC). The purpose of the eighteen-
member commission was to make recommendations to the National Science and
Technology Council and other government entities on bioethical and behavioral
research. The NBAC focused its efforts on protecting the rights and welfare of hu-
man research subjects. In addition, it managed information, genetic privacy and
confidentiality, and gene patenting.
In February 1997 President Clinton requested that the NBAC thoroughly re-
view the legal and ethical issues associated with the development of techniques to
clone sheep, and in May of 1997 the President extended the NBAC's charter until
1999.
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THE GENETICS REVDLUTIDN
Social Implications of rDNA Technology
Social implications erupted when rDNA technology was in its infancy In a rela-
tively short time, rDNA technology had a major impact on the knowledge of
the structure and function of genes. Today, rDNA technology and the rest of the
biotechnology industry are where the petrochemical and nuclear industries were
over half a century ago. The experiences in those fields have been extremely
valuable.
The recent contribution of rDNA technology to the health of people world-
wide cannot be questioned. Potential uses of rDNA technology in virtually every
area of medicine, biology, and agriculture seem even more promising now than be-
fore. It is difficult for this author to envision a disease or ailment that could not be
treated or cured by rDNA technology. In addition, rDNA technology has pro-
vided a way to isolate large quantities of specific segments of DNA in pure form.
With that knowledge, rDNA techniques have provided understanding of anti-
biotics, vitamins, and hormones, as well as medically and industrially useful
chemicals.
A newly approved genetic test may soon eliminate the guesswork in prescrib-
ing many drugs. The AmpliChip CYP450 has been cleared for use by the U.S.
Food and Drug Administration and will be used in June 2005. It is the first test to
allow doctors to tailor medication doses to a patient' s genetic makeup. The
matchbox-size device was developed by Roche Molecular Systems, a division of
Swiss pharmaceutical giant F. Hoffmann-LaRoche. Instead of circuits, the chip
contains millions of DNA molecules to analyze genetic material from a patient' s
blood. DNA is extracted from the patient' s blood and applied to the chip. A
computer scans the chip and generates a detailed report.
The AmpliChip CYP450 zeros in on two genes, 2D6 and 2C19, which regu-
late the enzymes that the liver produces to metabolize certain drugs, including the
breast cancer drug tamoxifen, antidepressants, beta blockers used for hyperten-
sion, anti seizure medications, and others. In addition, the test can identify the
rate at which drugs are cleared from a person' s body. The test has the potential to
determine how well a person will do on a specific drug.
At one time, there was a charge that DNA technology would lead to genetic
stigmatization and that rDNA technology would divert funds and attention from
much-needed health needs. One example shows that this is not true is sickle-cell
anemia, found mainly among black people, and which can be diagnosed in utero
only by DNA technology. Overall, few, if any, have raised the issue of "stigmati-
zation" with regard to sickle-cell anemia or other genetic diseases diagnosed by
rDNA technology
As rDNA technology grew, the U.S. government had to decide whether it
should take control of the technology, particularly since public funds supported
the basic research that had originally spawned rDNA technology. As a result, it
became increasingly necessary to see that social priorities were set up so that the
public would gain the advantages of rDNA technology. This was particularly nec-
essary because if social priorities were not set, the public would lose some im-
portant applications of rDNA technology, simply because private companies
found them unprofitable. During this time, many questioned whether and why
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the free market should decide which genetically altered organisms were pro-
duced.
Several important questions surfaced, including but not limited to:
Would new genetically altered agricultural products be priced so that small
farmers could take advantage of them?
Would society be protected from inadvertent secondary impacts of new prod-
ucts and processes, an ever-increasing reliance on drugs, or changes in the de-
pendency on chemicals for agriculture?
What ethical considerations would be applied when considering the treatment
of disease or in conjunction with reproductive experimentation?
The U.S. government determined that social responsibility for developing
rDNA technology also involved the Third World. Most scientists agreed that the
United States should share with those countries the benefits of the new technol-
ogy, aware that neglecting the needs of Third World economic systems and start-
ing a cycle of negative feedback would leave those countries even more
dependent on developed nations for aid. However, U.S. scientists were also con-
cerned that cultural norms of Third World countries not be hurt or destroyed
nor their capacity for self-determination inhibited.
Biological Warfare
As the United States and the Coalition continue to wage aggressive action against
world terrorism, many ask: What assurances do we have that rDNA technology
will not be used in the development of weapons for biological warfare? The bio-
logical, chemical, and nuclear weapons scenario reminds us once again of how
well-intentioned scientific advances, such as rDNA technology, may grant human
beings such vast powers that they endanger our fundamental political and social
values. Such power has haunted the development of rDNA research since its in-
ception in the 1970s. Recent completion of the Human Genome Project (HGP)
has made it possible to determine microbial gene sequences and to discover in-
formation we never before thought possible.
Whereas some have hailed rDNA technology as a huge step for molecular ge-
netics responsible for creating insulin, interferon, and other medications, others
fear it has opened a Pandora' s box. Some question whether rDNA technology is
a rash act with unpredictable consequences and an instrument that the strong
may impose on the less powerful. Opponents demand assurances that the tech-
nology will not be used for biological warfare or for sinister abuses of biophar-
maceutics by evil dictators.
We can look back and evaluate the 1975 Asilomar Conference that began as a
scientist's strategy conference and evolved into a public-policy process involving
not only 150 scientists but also a small group of lawyers and journalists. One of the
most consequential criticisms of Asilomar was that it was public decision making
without appropriate public accessa power play by special interest groups.
3 1
THE GENETI CS REVDLUTI DN
Yet, in retrospect the primary motive for the conference was biohazard (risk).
Perhaps the greatest potential for biohazard was related to possible military ap-
plications. At that time, panel members suggested an international treaty to pre-
vent their construction.
27
Others wondered if the NIH Quidelines were strong
enough to hold the military establishment accountable. After considerable dis-
cussion, it was concluded that unless nations were willing to forgo some of their
rights of sovereign immunity, it was doubtful that adequate verification would be
possible under even the best of guidelines.
The major controversy over rDNA technology centered around unforeseen
risksfor example, whether microorganisms that were genetically modified in a
lab might escape and become dangerous to the general population. Other con-
cerns were raised; however, organizers decided to concentrate entirely on the risk
of escape. The problem was exacerbated because scientists not only were unable
to quantify the odds of harm occurring; they could not predict the type of harm
that might occur.
At the time, the possible release into the environment of designer microor-
ganisms was known to be very real, creating an important debate over safety. In
1987 a statement was issued by the Scientific Committee on Problems of the En-
vironment and the Committee on Genetic Experimentation: "The environmental
introduction of any organism should be undertaken within a framework that
maintains appropriate safeguards for the protection of the environment and hu-
man health while not discouraging innovation."
28
We know well the possibilities of such an undertaking in the hands of dicta-
tors such as Iraq's past leader, Saddam Hussein. Genetically designed microor-
ganisms can be made even more efficient than natural diseases at killing and
disabling the enemy. In the past, Saddam Hussein and others have used ethnic
weapons (pathogenic microorganisms that have been genetically modified) to in-
fect and kill racial and ethnic groups.
Recent advances in rDNA research and terrorism worldwide have made pos-
sible genetically transformed organisms ("designer bugs") packed with genes that
simultaneously signal millions of human cells to commit suicide or wipe out
the human immune system. Microorganisms that cause smallpox, botulism,
tularemia, cholera, Q fever, and brucellosis are long-standing lethal favorites of
bioweaponeers such as Dr. Hudah Ammash of Iraq, trained as a microbiologist in
the United States and a prominent member of Saddam Hussein' s inner cabinet.
In effect, scientists such as Dr. Ammash are able to modify ordinary microbes,
turning them into extra-virulent, drug-resistant superbugs. Such modifications of
microbes make them harder to detect, diagnose, and treat, but they are also more
useful militarily.
Various other countries have been successful in creating "designer bugs." For
example, Russian researchers in 1987 created a new form of anthrax. Funded by
six federal agencies on the heels of the Human Genome Project, the new altered
form of anthrax was developed at the State Research Center for Applied Micro-
biology in Obolensk, Russia. The research was formally published in December
1997 in the British scientific journal Vaccine.
It is unclear why the Russian researchers developed the new organismwhether
it was for offensive or defensive purposes. At the time, the Russian Federation was
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a signatory to the 1972 Biological Weapons Convention banning the develop-
ment, production, and stockpiling of biological and toxin weapons. The Conven-
tion had no provisions for enforcement; however, the UN Secretary-General
possessed the authority to investigate complaints of violations.
Development of a new strain such as the Russian anthrax through rDNA
technology is something that biological warfare experts around the world have
feared since the advent of rDNA technology. Currently, a dozen or more coun-
tries are believed to have the capacity to load weapons with dry, powdered an-
thrax, a disease that can cause severe illness and death in humans and animals
who inhale the spores in large doses.
In assessing the risks of rDNA technology, society must decide whether the
burden of proof will be on those who demand evidence of safety, or on those
who demand evidence of hazard. The former countries will halt experiments un-
til they are proven safe, whereas the latter countries will continue until they are
proven harmful. Unless certain nations are willing to forgo some of their rights
of sovereign immunity, it is doubtful that adequate verification would be possible
under even the best of guidelines.
As public and private individuals, most people strive to better their lives ma-
terially, biologically, intellectually, and emotionally. As a society, humans with
knowledge of rDNA can, with various resources, promote their perception of a
common good. Even more so, we can strive to make the world a better place for
all societies.
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3
THE BDDK DF LI FE
The Human Genome Project
None of us so privileged few who first saw the double helix in the
spring of 1953 ever contemplated that we might in our lifetime
see it completely decoded.
James Watson, Nobel laureate and
codiscoverer of the DNA double helix
In April 2003 the Human Genome Project (HGP), also known as the "Book of
Life" and the "Human Genome Initiative" was completed to an accuracy of 99.9
percent, coinciding with the fiftieth anniversary of Watson and Crick' s elucida-
tion of DNA. A rough draft of the human genome was partially completed in the
year 2000, but that draft included thousands of gaps in the long sequence of
DNA base pairs. With the April 2003 completion, only 400 gaps remained open,
down from 250,000.
The human genome (the total amount of genetic material in a cell) is com-
posed of about three billion pairs of DNA chemicals. The genes that control the
body' s growth, development, functions, and aging are made of specific sequences
of these chemical or base pairs. Even a small change in one or more of these se-
quences may cause disease.
Spectacular Project
The HGP was a multinational project aimed at obtaining a detailed map and a
complete sequence of the human genome. The human DNA used for the HGP
was almost exclusively from people of Europe or Nort h America because those
THE GENETI CS REVDLUTI DN
were the places where most HGP researchers lived. When the preliminary com-
pletion of the HGP was announced it was viewed as a spectacular event, one that
exceeded expectations. "The newly completed sequence of the human genome is
now on parade for the whole world to see. However, it may be as striking for what
we don' t see as what we do."
1
The HGP was hailed as the largest and most expensive study of biology con-
ducted since the Apollo project and the race to send a human to the moon. Not
only the U.S. government but governments around the world raced to map the
location of what was then estimated to be 100,000 genes on chromosomes. Bil-
lions of dollars were devoted to the project.
Inclusion of the word "human" in the name Human Genome Project does
not accurately reflect the initiative, however, because the HGP was not exclusively
a study of humans. The first genome project completed was that of the bacterium
Haemophilus influenzae. Since then, the genomes of several other well-known or-
ganisms have been examined along with those of humans, including the common
intestinal bacterium (Escherichia coli); yeast (Saccharomyces cerevesiae), the first eu-
caryotic genome completed in 1996; the fruit fly (Drosophila melanogaster); the
roundworm (Caenorhabditis elegans); and the laboratory mouse.
In particular, the mouse genome has provided an excellent approach to inter-
preting human genomic information, because many genes were conserved between
the two species, as was gene order along some chromosomes. The mouse genome
is about the same size and 85 percent identical to the human genome. Such infor-
mation was deemed useful because it aided in the identification, characterization,
and understanding of genes that directly and indirectly lead to human disease.
The International Mouse Mutagenesis Consortium has created approximately
5,000 mutant mouse strains carrying genes for diseases resembling human dis-
eases such as sickle-cell anemia and colorectal cancer.
A Solid Foundation
Watson and Crick' s discovery of the helical structure of DNA in April 1953 and
the explosive development of cytogenetics from 1959 and somatic cell genetics
from 1964 provided a solid foundation on which progress toward a human gene
map could be made. These scientific discoveries, followed by the advent of rDNA
technology in the early 1970s, made it possible to think of isolating individual
genes. Those breakthroughs, combined with powerful DNA sequencing tech-
niques developed by Allan Maxam and Walter Gilbert at Harvard University and
Frederick Sanger at the United Kingdom' s Medical Research Council (MRC),
provided the technological basis for the HGP.
In 1980 David Botstein of the Massachusetts Institute of Technology, Ronald
Davis of Stanford University, and Mark Skolnick and Ray Whi t e of the Univer-
sity of Utah, proposed a method to map the entire human genome. Recombinant
DNA (rDNA) technology enabled the cloning of DNA fragments. By 1985 the
technology scientists were able to extract individual X and Y chromosomes.
In 1986 the phenomenon of gene shuffling ("genes that jump") was announced
by Dr. Barbara McClintock, proving that the genome was unstable. In 1960
3 6
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McClintock had come across a paper, coauthored by Francois Jacob and Jacques
Monad, published in a French journal. Jacob and Monad had proposed a system
called the "operon" that was composed of a structural gene and a regulator gene.
2
McClintock won the Nobel Prize for her workthe first woman to win it alone
for medicine.
Detailed human genetic mapping and family pedigree analysis, a very impor-
tant tool for the analysis and diagnosis of human genetic diseases, was initiated in
1986, allowing genes to be identified quite rapidly. The same year, Duchenne and
Becker's muscular dystrophy genes were identified, entering a new era of medical
treatment and diagnosis. About the same time, construction of an E. coli clone
library was begun in order to analyze the E. coli genome. This included the con-
struction of artificial chromosomes that replicated in yeast, allowing large frag-
mentation of genes.
3
Small groups throughout the world worked to find chromosome markers for
linkage analysis. Two groups, under the direction of Ray White at the University
of Utah' s Howard Hughes Medical Institute and Helen Donis-Keller at Collabo-
rative Research outside Boston, began large-scale efforts. In 1987, the Donis-
Keller group published a linkage map of the human genome.
4
In 1988, the DNA
polymerase chain reaction (PCR) was introduced, allowing rapid amplification of
short regions of DNA with great ease.
5
A Short History of the HGP
The HGP was widely discussed within the scientific community and public press
during the last half of the 1980s. When Robert Sinsheimer, then chancellor of
the University of California at Santa Cruz, first got the idea to determine the
complete nucleotide sequence of the human genome in 1985, he decided to invite
some of the world's best scientists to the Santa Cruz campus. Among those invited
to the May meeting were genetic mapper David Botstein of the Massachusetts
Institute of Technology (MIT); Robert Waterston of Washington University in
St. Louis; John Sulston of Cambridge University; Bart Barrell, head of the se-
quencing unit at the MRC; Helen Donis-Keller of Collaborative Research, Inc.;
sequencing experts George Church and Walter Gilbert of Harvard University;
and Leroy Hood of the California Institute of Technology in Pasadena.
There were some skeptics among the outstanding scientists at the Santa Cruz
meeting. One of the skeptics was Hood, who thought the proposed HGP seemed
to be a huge science project with minimal value to the science community. Nobel
laureate David Baltimore, then director of MIT' s Whitehead Institute, and Bot-
stein were among others who expressed doubts about the project. They feared that
such an extensive project would have the same impact on science that the shuttle
had on the space programtaking away significant amounts of money and scien-
tific talent from smaller, yet vital, projects.
Others questioned the value of undertaking a complete sequencing of the
genome, especially given the high proportion of noneugenic sequences. The HGP
evoked various questions, which included invasion of privacy, abortions, discrim-
ination of the unfit, the right to know, and eugenics.
6
3 7
THE GENETI CS REVDLUTI DN
Despite some skepticism at the initial meeting to discuss the HGP, partici-
pants gave strong support to proceeding with the complete sequencing of the hu-
man model-organism DNA. Not surprisingly, a major concern was financing.
Even so, most participants felt that there was technology enough to complete the
HGP in reasonable time and at a reasonable cost. Overall, participants at the
meeting felt that the proposed research was critical, that genomic sequence for
most model organisms was cost effective, and that the proposed overall HGP
goals were attainable. Dr. James Watson, Nobel laureate and codiscoverer of the
double-helical structure of DNA, was singled out as the movement' s most distin-
guished and creditable advocate.
Participants at the initial meeting felt that the Department of Energy (DOE)
and the National Institutes of Health (NIH) should be the main research agencies
within the U.S. government responsible for developing and planning the HGP. The
NIH had a long history of supporting research in genetics and molecular biology,
as well as having the integral mission of improving the health of all Americans.
However, the possibility of a highly visible health-related program operated by the
DOE proved both irritating and stimulating to some individuals at the NIH.
In addition to genome research programs at NIH and DOE, other U.S. groups
were involved in the HGP project from early on: the Howard Hughes Medical In-
stitute (HHMI), the National Science Foundation (NSF), and the Department of
Agriculture. HHMI had a particularly strong interest in genetics and employed
some of the best human genetics investigators in the United States. The DOE had
earned a reputation as a credible player in genome work on chromosome sorting,
computer-based DNA sequence informatics, and mouse genetics. Yet, despite their
long-standing program of genetic research directed at improving the ability to as-
sess the effects of radiation and energy-related chemicals on human health, many
questioned why was the DOE was involved in the HGP.
Some pointed out that the problem of detecting inherited mutations in hu-
mans had worried the DOE since the Manhattan Project and the U.S. use of atomic
bombs against Japan at Hiroshima and Nagasaki in August of 1945. A meeting had
been held in Alta, Utah, in December 1984 to assess how direct analysis of DNA
might be useful in detecting mutations among atomic bomb survivors.
7
'
8
As part of
the planning process for the DOE program, Los Alamos National Laboratory or-
ganized a workshop in Santa Fe, New Mexico, in March 1986 to discuss plans to
sequence the human genome. Workshop participants were enthused about the pro-
posed DOE Human Genome Initiative and endorsed the HGP.
The first published proposal for the HGP was an independent editorial by
Renato Dulbecco, President of the Salk Institute at San Diego, in which he sug-
gested that the fundamental problem of cancer could be studied by first deter-
mining the sequence of the entire human genome. Dulbecco' s proposal was
published the same week in March 1986 as the Santa Fe meeting.
9
In June 1986 at the Cold Spring Harbor symposium on the Molecular Biol-
ogy of Homo sapiens, Walter Gilbert and Paul Berg cochaired a session on the
HGP. Both Berg and Gilbert voiced substantial enthusiasm for a genome project
growing out of the Santa Cruz and Santa Fe meetings. However, once again there
was a great deal of skepticism voiced as to whether the DOE was the appropriate
agency to direct such an effort. Others questioned whether a sequencing research
3 8
THE BDDK DF LIFE
project made technical sense. Because of its acrimonious tone, the meeting and
its participants received widespread scientific press attention. As a result of in-
tense interest, the National Research Council (NRC) of the National Academy of
Sciences commenced a study in late September 1986.
Soon after the Cold Spring Harbor meeting, several other meetings were
scheduled near Washington, D.C., to discuss the HGP. Two of these were large in-
ternational meetings attended by invited participants. The first was convened in
August by the HHMI and was intended to discuss whether and how HHMI might
contribute to a large international genome project.
10
Another meeting was held
by the NIH in October to discuss the HGP' s primary role.
11
The NRC met several times during 1987 and issued a report in February 1988
that argued strongly for a broader HGP. Bruce Alberts, the committee chair, had
in 1985 written an editorial highly critical of big science in biology.
12
The com-
mittee included several members who were very skeptical of genome proposals.
Nonetheless, they were convinced of the merits of the HGP and forged a consen-
sus by embracing work on nonhuman organisms and genetic linkage mapping.
After deliberations, committee members recommended a new, dedicated genome
research budget of $200 million per year for fifteen years. In the spring of 1987, a
Report on the Human Qenome Initiative was prepared by the Health and Environ-
mental Research and Advisory Committee (HERAC) of the DOE.
By 1988, the DOE and NIH were working together in a fairly harmonious rela-
tionship that resulted in the publication of two widely circulated, influential re-
ports. The House Committee on Energy and Commerce commissioned a report by
the Office of Technology Assessment (OTA). Released in April 1988, the OTA re-
port presented a comprehensive and detailed analysis of the scientific develop-
ments that had led to mapping and sequencing the human genome. The OTA
report noted that the debate over the HGP was not about whether the research
should go forward, but how it should be managed and who should coordinate it.
The publication presented a number of options as to how the United States might
pursue such a project.
13
The second publication, the National Research Council Report, recommended
that the United States support the human genome research effort. The report
outlined a multiphase research plan for sequencing human DNA over two de-
cades. A report to the director of the NIH by the Ad Hoc Advisory Committee
on Complex Genomes, also prepared in 1988, concurred with the NRC report.
At the time the NRC and OTA reports were written, the scientific community be-
lieved that the art technology was sufficient to develop detailed genetic maps, but
only limited physical maps of the HGP, because the genome was so large and
complex.
The scientific community continued to have concerns that there was not
technology available for DNA sequencing the estimated three billion base pairs
of human DNA. Because of this, the NRC committee and others recommended a
multiphase program. Charles DeLisi of the DOE was very enthused about the
HGP and conceived of a three-pronged research program that advocated ad-
vanced DNA sequencing technology, computer analysis, and methods to order
DNA fragments cloned from the human genome. In 1987, DeLisi began a re-
search program focused on these objectives and called the DOE Human Genome
3 9
THE GENETI CS REVDLUTI DN
Initiative. This was the first government program on genome research, and it suc-
cessfully catalyzed a vigorous debate in the United States and other nations.
14
By 1988, the DOE and NIH were making substantial scientific progress. Their
solid relationship was formalized by the signing of a Memorandum of Under-
standing to "coordinate research and technical activities related to the human
genome."
15
That same year, the U.S. Congress appropriated funds to both the
DOE and the NIH for research efforts to determine the structure of complex
genomes. In addition, the U.S. Congress also requested the NIH to prepare, by
early 1990, a report on the optimal strategy for the conduct of the HGP; and the
FY 1990 House Appropriations Committee Report asked the NIH for a compre-
hensive spending plan which was to be completed in time for the FY 1991 appro-
priation hearings.
16
In March 1988, NIH director James Wyngaarden, at a meeting held in Re-
ston, Virginia, announced the creation of a special office for genome research.
This was followed in June 1988 by the first annual genome meeting at Cold
Spring Harbor Laboratory. In September 1988 the NIH established the National
Center for Human Genome Research and appointed Nobel laureate James D.
Watson as its head. Watson announced that 3 percent of the genome budget
would be devoted to studies of social and ethical issues and that the primary goal
of the first stage of the project would be to build maps of the human chromo-
somes. Watson declared that the project would be completed in five years. With
his appointment and substantial leadership, the NIH moved ahead of the DOE.
In October 1988, prior to the actual start of the HGP, a Workshop on Inter-
national Cooperation for the Human Genome Project was held in Valencia, Spain.
Fearing hazards that might lead to "Nazi-like atrocities," French researcher Jean
Dausett asked for a moratorium on genetic manipulation of germ cells and on
gene transfer experiments in embryos. However, Nort on Zinder of Rockefeller
University argued that the workshop had no actual authority to make the mora-
torium stick. As a result of Zinder's arguments, workshop participants drafted a
resolution that called for international cooperation for the project.
17
At the meeting, participants supported Director-General Frederico Mayo' s
initiative and agreed that the United Nations Education, Scientific, and Cultural
Organization (UNESCO) could help facilitate international cooperation. Follow-
ing the workshop, Dr. Mayo assembled an advisory group of scientists to con-
sider the role that UNESCO might play in the advancement of the HGP.
18
In January 1989 Zinder chaired the first program advisory committee meeting
of the HGP. At that time, scientists quickly moved ahead by initiating the $3 bil-
lion HGP project, with the ultimate goal of detailing the entire genome. In addi-
tion, the U.S. Congress in 1989 approved $53 million following Watson' s plea for
financial support for the HGP. In October the NIH office was elevated to the Na-
tional Center for Human Genome Research (NCHGR), with grant-awarding au-
thority.
A mont h later, the first NCHGR meeting was held in Paris. Overall, the DOE
and NIH developed a well-integrated plan for carrying out the HGP initiative.
During that time, the two agencies established joint working groups on mapping,
informatics (dealing with databases and computational analysis), and social, ethi-
cal, and legal implications of genome research. The two agencies also agreed to
4 D
THE BDDK DF LIFE
notify one another about funding decisions regarding grant proposals reviewed
by both agencies.
In 1990-91 a program on the HGP was subsequently approved by the partic-
ipants at the Twenty-fifth General Conference. Dr. Frederico Mayo set up a Sci-
entific Coordinating Committee (SCC) to help plan and implement the program
as proposed in the Moscow recommendations. The first meeting of the SCC was
held at UNESCO headquarters in Paris, France, on February 1, 1990.
A second consultative meeting was held in Moscow the following June in par-
allel with the Human Genome Organization (HUGO). At that meeting a number
of conclusions were reached: first, full knowledge of the human genome was of
vital importance and the medical, technological, scientific, and ethical implica-
tions of the program were inseparable; second, establishment of the program
should be supported by governments; third, the influence of international organ-
izations such as UNESCO and HUGO was recognized; and finally, it was ac-
knowledged that UNESCO was in a unique position to promote interest in the
HGP in developing countries.
In April 1990 NIH and DOE together submitted a publication of a five-year
joint research planan unprecedented accomplishment.
19
In August 1990 the
NIH began large-scale sequencing trials on four model organisms, and the two
agencies declared October 1 to be the official beginning of the HGP.
Meanwhile, scientists were making substantial progress in their genome stud-
ies. By 1990, Sulston and his Cambridge University team were nearing comple-
tion of the physical map of the worm, and Maynard Olson and his team at the
University of Washington-Seattle, were making progress on mapping yeast genes.
In June 1991 Craig Venter, who ran a sequencing lab at the National Institute for
Neurological Disorders and Stroke, announced that he and his colleague Mark
Adams had developed a new technique (expressed sequence tags) that enabled
them to quickly find genes. Venter and his colleagues also announced plans to
patent the genes that they had found. However, at a congressional hearing, Wat-
son called Venter's proposed patent "sheer lunacy" and a fight erupted. As a result
of the disagreement, the NIH eventually withdrew its patent application.
Venter left his position at the NIH in 1991 and with his second wifeClaire
Fraser, a prominent molecular biologistformed The Institute for Genomic
Research (TIGR), a nonprofit company in Rockville, Maryland. They obtained
long-term funding of $70 million from biotech entrepreneur Wallace Steinberg,
with the understanding that any genes the company decoded would go to Human
Genome Sciences, a company led by former AIDS researcher William Haseltine.
Meanwhile, at the NIH, Watson was fighting with his boss, Dr. Bernadine Healy.
As a result of that dispute, Watson left his job and returned to the Cold Spring
Harbor Laboratory in April 1992.
On May 12-15, 1992, the First South-North Genome Conference was held in
Caxambu, Brazil. Approximately 200 participants from 22 countries assembled
to design strategies that would enable developing nations to participate in the
HGP. Main conference sponsors were UNESCO and the Brazilian Society of Bio-
chemistry and Molecular Biology. Sergio Pena of the Federal University of Mi-
nas Gerais chaired the organizing committee. A number of international and
Brazilian agencies provided financial support.
4 1
THE GENETI CS REVDLUTI DN
In October 1992 U.S. and French scientific teams completed the first physical
maps of chromosomes. David Page and his colleagues at the Whitehead Institute
mapped the Y chromosome, and Daniel Cohen and his colleagues of the Centre
d'Etude du Polymorphisme Humain (CEPH) and Genethon mapped chromosome 21.
In April 1993 Francis Collins of the University of Michigan-Ann Arbor was
named director of NCHGR. Recognized as a very successful scientist, Collins
had discovered the genes for cystic fibrosis, Huntington' s disease, neurofibro-
matosis, and a form of inherited breast cancer.
On April 23-24, 1993, the NIH NCHGR held a meeting in Hunt Valley,
Maryland. At that time, participants decided on a number of topics: first, to ap-
praise project accomplishments that were likely to be achieved by the end of the
initial five-year phase; second, to generate creative and novel ideas for building on
this progress to meet long-range goals; and third, to consider ways in which the
project could most effectively and broadly benefit present and future research in
biology and medicine.
In October 1993 the NIH and DOE published a five-year revised plan
(1993-98) that included completing the human genome by 2005. That same
mont h the GenBank database officially moved from Los Alamos to the National
Center for Biotechnical Information (NCBI), ending the NIH' s and DOE' s battle
over control. In September 1994 Jeffrey Murray of the University of Iowa and
Cohen and his colleagues at Genethon published a complete linkage map of the
human genome.
The year 1995 proved to be very productive for the HGP. Sequencing dyes were
developed in mid-1995, and in August thermostable polymerase was developed. In
July 1995, Craig Venter, Claire Fraser, and Rob Fleischmann of TIGR, along with
Hamilton Smith at Johns Hopkins University, published the first sequence of a
free-living bacterium, Haemophilus influenzae. The accomplishment, they reported,
was done in twelve months using a bold new approach, whole-genome shotgun
sequencinga procedure that previously had been rejected by the NIH.
In October 1995 Patrick Brown and his team at Stanford University pub-
lished their first paper describing a printed glass microarray of complementary
DNA (cDNA) probes. In December Eric Lander and Thomas Hudson published
a physical map of 15,000 markers in the human genome, and by the end of 1995
the Japanese government had funded several sequencing groups at the University
of Tokyo, Keio University, and Tokai University.
In February 1996, at a conference in Bermuda funded by the Wellcome Trust,
it was agreed that sequence data would be released into public databases. This was
followed in April of that same year with funding of six groups by the NIH for
large-scale sequencing of the human genome. The DOE also initiated six pilot
projects, funded at a total of $5 million. In October 1996 an international consor-
tium publicly released the complete genome sequence of the yeast Saccharomyces
cerevisiae, and in November Yoshide Hayashizaki's group in Japan completed the
first set of full-length muscle cDNAs.
January 1997 saw the NCHGR promoted to the National Human Genome
Research Institute,
20
and the DOE created the Joint Genome Institute. In Septem-
ber of that year, the DNA sequence of the bacterium E. coli was completed by
Guy Plunkee and Fred Blattner at the University of Wisconsin at Madison. In
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THE BDDK DF LIFE
February 1998 representatives of the United States, Japan, the European Union,
China, and South Korea established guidelines for an international collaboration
to sequence the rice genome.
An Intense Feud
In May 1998, just days before the annual meeting of genome scientists at Cold
Spring Harbor Laboratory, an intense scientific feud erupted between Francis
Collins, director of the NIH' s National Human Research Institute (NHGRI) and
the HGP' s official head, and J. Craig Venter, CEO of Celera Genomics, an inde-
pendent genome-sequencing company.
Venter announced that his newly formed company, Celera Genomics, planned
to sequence the human genome within three years, at a price approaching $300
million. This was possible, he said, because Celera had teamed with Perkin-Elmer
Corporation, which had designed the whole genome shotgun fragmentation
method. The HGP team, on the other hand, was more conservative, saying that it
planned to use landmark maps. At about the same time, the Wellcome Trust an-
nounced that it was doubling its financial support for the HGP to $330 million,
amounting to about one-third of the sequencing.
Venter and Collins were both deeply involved in sequencing DNA. Their main
differences centered around who should get credit from the scientific community
for the DNA sequencing. Venter had made a number of enemiesin addition to
his feuding with Collins, he had angered James D Watson. Addressing a Senate
hearing panel, Watson referred to Venter's work as sloppy and nonscientific, and
implied that the new instrumentation made possible by Celera "could be run by
monkeys." (Later, however, Watson recanted his statement.) Others, including
William Haseltine, CEO of Human Genome Sciences and a partner of Venter's un-
til 1997, accused Venter of egotistical motives in decoding the human genome.
In September 1998 Collins, on behalf of the NIH and DOE, announced they
were moving the completion date of the HGP draft from 2005 to 2003; and in
December John Sulston of the Sanger Centre and Robert Waterston of Washing-
ton University completed the genomic sequence of the organism Caenorhabditis
elegans.
With no visible signs of the feud ending, in July 1999 Eric Lander of the
Whitehead Institute offered to mediate a truce between Collins and Venter. In
December 1999 they met at Celera headquarters; however, a truce could not be
affected. Another attempt at a truce was planned. In March 2000, Anthony
Fauci, director of the National Institute of Allergy and Infectious Diseases, and
Richard Klausner, director of the National Cancer Institute, met with Collins and
Venter in Bethesda, Maryland. Once again, an agreement could not be reached.
The NIH launched a project in September 1999 to sequence the mouse
genome, devoting $130 million over three years. In December U.S., British, and
Japanese researchers completed the first sequence of chromosome number 22.
The NIH again moved the rough draft to spring 2000, and by March 2000 Celera
and its collaborators had sequenced the genome of the fruit fly, Drosophila
melanogasterthe largest genome yet sequenced. This was highly significant
4 3
THE GENETI CS REVDLUTI DN
because D. melanogaster is an organism whose genes have many counterparts in
humans. Wanting to show off his shotgun method of sequencing, Venter teamed
with Gerald Rubin and his team at University of California at Berkeley.
The feud continued to intensify with no signs of resolvement until on April
7, 2000, President Clinton issued a proclamation for the feud to end. On April
10, Aristides (Ari) Patrinos, a mediator at HGP' s DOE, requested a meeting be-
tween Collins and Venter in neutral territory. On May 7, 2000, Collins and Ven-
ter met at Patrinos's town house, but still they could not come to an agreement.
A second meeting at Patrinos's home ended in an informal agreement that Venter
and Collins would coordinate their announcements. However, they did not agree
to face the press together.
Venter and Collins met again, once on May 30, 2000, and again on June 21,
2000, at Patrinos's home. At this time, Collins and Venter finally came to a work-
able agreement that each would get credit for sequencing and deciphering all 3.1
billion biochemical "letters" or base pairs of human DNA. In addition, they
agreed to publish their work simultaneously in a major journal. (Eventually, how-
ever, each published in different journals, Venter in Science and Collins and HGP
in Nature.) They also agreed to stop criticizing each other publicly.
Goals of the HGP
The original HGP plan consisted of a set of specific goals for the first five years of
the research project that focused the efforts of the research community on the
most important initial objects.
21
Overall project goals were to:
identify all the estimated 100,000 genes in human DNA
determine the sequences of the 3.1 billion base pairs of nucleotides that made
up the twenty-three human chromosomes that comprised the human genome
store the information in databases, develop tools for data analysis, and
address the ethical, legal, and social issues that might arise from the project.
Four subgoals were also determined. The first subgoal was a comprehensive
genetic map based on pedigree analysis. The second subgoal was a physical map of
the distances between genes. (This was measured using the tendency of a gene to
link to those around it.) The third subgoal was a transcript map of the location
of genes in the human genome. The fourth subgoal was the gene sequencea list of
base pairs that made up a specific gene.
When the initial goals were adopted in 1990, it was understood that achiev-
ing them would require a significant degree of improvement in technology and
methodology in both molecular genetics and instrumentation. This would re-
quire improvements in storage, retrieval, and analysis of mapping and sequence
information (informatics) to make data usefully available as required. By Septem-
ber 1990 the sequences of over 5,000 human genes had been realized, as well as
the location of 1,900 genes to areas of specific chromosomes.
22
4 4 -
THE BDDK DF LIFE
The 1990 plan was updated in 1993 by extending the initial goals of genome
research through September 1998. Designed to address both long-and short-term
needs, the updated plan extended research goals in established categories. It also
added specific new goals for developing technology for gene identification and
mapping. This included mapping and sequencing the human genome; mapping
and sequencing the genomes of model organisms; data collection and distribu-
tion; ethical, legal, and social considerations; research training; and technology
development and transfer.
23
Funding the HGP
In the late 1980s, Congress appropriated funds to the NIH and DOE to establish
the HGP and map genetic information. A portion of the funding was directed to
establish the Ethical, Legal, and Social Issues (ELSI) program, a working group to
address the legal, ethical, and social ramifications associated with the HGP. As a
result, the HGP made a commitment to devote approximately 5 percent of its
budget to research aimed at anticipating and resolving the ethical, legal, and so-
cial issues that might arise from the genome research.
The United States took the lead with goals of as much as $200 annually ad-
justed for inflation.
24
'
25
Although this amount was assumed when the initial goals
were developed and implemented, appropriations never reached that level. Total
funding rose from about $47 million in 1987 to around $182 million in 1995.
U.S. Genome Centers and Programs
Large-scale sequencing of the HGP became concentrated in a small number of
genome centers and programs in the United States. In 1989 the National Center
for Human Genome Research (NCHGR) was one of twenty-four institutes, cen-
ters, or divisions established by the NIH. The NCHGR had several administrative
units in its organizationthe Office of the Director, the Division of Extramural
Research (DER), and the Division of Intramural Research (DIR).
26
'
27
The NCHGR Division of Intramural Research also sponsored a number of stu-
dent training programs, including summer internships, post-baccalaureate trainee
ships and a graduate program in genetics at George Washington University. The
NCHGR supported numerous grants aimed at cultivating minority participation
in genome research, such as the minority travel awards and the minority research
supplements. These programs impacted a wide range of participants, since they
were aimed at both students and faculty members. By disseminating information
about the HGP and its technologies across the country, NCHGR hoped to foster
minority student interest and participation in genetic research.
The Ethical, Legal, and Social Implications (ELSI) Branch was responsible for
research to analyze the legal, ethical, and social issues that arose from human
genome research and to ensure that the information was used responsibly. In ad-
dition, ELSI fostered research and programs to improve public and professional
education with regard to ethical, legal, and social issues.
4 5
THE GENETI CS REVDLUTI DN
The Mammalian Genomics Branch was responsible for research directed to
the construction of complete genetic and physical maps of individual mam-
malian chromosomes and genomes. In addition, it was responsible for accurate
sequencing of large (megabase) regions of mammalian DNA. This branch was
also responsible for the administration and support of research in genome infor-
matics, including database research, development and maintenance of databases
of genome information, and research into techniques for genomic analysis. The
Mammalian Genomics Branch also supported policy development for the
Genome Science and Technology Centers (GESTEC) program.
The Mapping Technology Branch was responsible for the development of
technology to improve the resolution, information content, and utility of ge-
nomic maps, including both genetic maps and physical maps. Specific areas of in-
terest included new or improved methods for the construction and annotation of
genetic and physical maps, and techniques and strategies for efficient identifica-
tion of genes, coding regions, and other functional elements on a high-throughput,
genome-wide basis. The Branch was also responsible for extramural training, career
development, and special programs. Accordingly, the branch planned and adminis-
tered programs of individual pre- and post-doctoral fellowships, institutional
training grants, career awards, minority programs, international programs, short
courses, and scientific meetings.
The Sequencing Technology Branch was responsible for research to develop
new methods, technologies, and instruments for fully integrated, innovative ap-
proaches to rapid low-cost determination of DNA sequence. Areas of interest
included both refinement and full automation of current methods of DNA se-
quencing and novel approaches to achieve order-of-magnitude improvements in
sequencing capability. The Sequencing Technology Branch also supported re-
search to develop maps and genomic DNA sequence of non-mammalian orga-
nisms. This branch was also responsible for technology transfer activities, and
promoted collaborative, multidisciplinary programs that closely integrated re-
search projects at academic and industrial laboratories.
The Diagnostic Development Branch focused on the molecular characteriza-
tion of human development disorders. This branch was specifically interested in
the mechanisms and consequences of chromosomal abnormalities that produced
specific mental retardation syndromes due to gene dosage imbalance and ge-
nomic imprinting effects. It used positional cloning strategies and genome tech-
nologies to clone and characterize specific chromosomal regions and genes
responsible for the disease phenotype.
The Human Genome Education Program (HGEP) operated within the Stan-
ford University Human Genome Center. It was a collaborative effort among HGEP,
Genome Center scientists, collaborating staff from other education programs,
experienced high-school teachers, and an advisory panel in the fields of science,
education, social science, assessment, and ethics. The primary objectives for
HGEP were to develop a human genome curriculum for-high school science and
to provide education outreach to schools and community groups in the San Fran-
cisco Bay area.
The Lawrence Berkeley National Laboratory' s Human Genome Educators
Program, sponsored by the Lawrence Berkeley National Laboratory' s Human
4 6
THE BDDK DF LIFE
Genome Program, was an information network of education professionals with
an active interest in all aspects of genetics research and education. This national
group included scientists, researchers, educational curriculum developers, ethi-
cists, health professionals, high-school teachers and instructors at college and
graduate levels, and others in occupations affected by genetic research. Genome
Educators was a unique collaborative effort dedicated to sharing information and
resources to further the understanding of current advances in the field of genetics.
International Genome Centers and Programs
In many countries worldwide, active genomic research was also being pursued by
researchers and science funding agencies at both public and private institutions.
Programs varied in the countries involved, depending on their particular con-
cerns, capabilities, and funding. Some of the larger programs, in addition to those
of the United States, were in Brazil, Canada, China, Denmark, the European
Union, France, Germany, Israel, Japan, Mexico, the Netherlands, Russia, Sweden,
and the United Kingdom. Several smaller countries also participated in interna-
tional collaboration with larger countries. In addition, the European Commis-
sion established a multinational, coordinated Human Genome Analysis program
to complement the various national initiatives in Europe.
28
The European Community (EC) played a significant role in the HGP. In 1988,
the EC introduced a proposal entitled the Predictive Medicine Programme. How-
ever, a few EC countries, notably Germany and Denmark, claimed the EC pro-
posal lacked ethical sensitivity Germany, in particular, had strong objections to
the possible eugenic implications of the program. Because of such controversy,
the initial proposal was dropped. However, it was later modified, renewed, and fi-
nally adopted in 1990 as the Human Genome Analysis Programme (HGAP).
The HGAP had three objectives: First, to provide an improved study of the
human genome for a better understanding of genetic functions and the preven-
tion and treatment of human disease; second, to establish medical, ethical, social,
and legal guidelines to ensure that the results of the research were not misused;
and third, to ensure that modification of human characteristics by genetic engi-
neering of germ cells and embryos is excluded from the program.
29
In 1989 the UK Secretary of State for Education and Science awarded 11
million ($21 million) to the Medical Research Council (MRC) for the initiation of
a national Human Genome Mapping Project (HGMP) to coordinate and expand
UK activities in human genome mapping and to provide a link with genome re-
search in other countries. Program objectives included giving the United King-
dom a role in international genome research and ensuring that the nation would
benefit from medical and commercial applications of genome work. The UK pro-
gram concentrated on identifying and isolating as many genes as possible and
characterizing them in biological terms.
30,31
The international scientific community involved in human genome work
formed the Human Genome Organization (HUGO) to coordinate the interna-
tional effort and to foster collaboration between scientists; to facilitate the ex-
change of data and biomaterials; to encourage debate on scientific, social, ethical,
4 7
THE GENETI CS REVDLUTI DN
legal, and commercial implications of human genome projects; and to ensure
that the results of research are freely available to all nations.
32
Mapping and Sequencing the Human Genome
Mapping of human genes began early in the twentieth century; however, it had
been extensively pursued only for the last few decades. The first meeting dedi-
cated specifically to discussing the feasibility of mapping and sequencing the hu-
man genome was held in May 1985 at the University of California at Santa Cruz
under the auspices of Robert Sinsheimer, Bob Edgar, Harry Noller, Bob Ludwig,
and colleagues.
In order to obtain sufficient quantities of DNA for study, it was necessary to
reproduce the DNA fragments of interest. One way that this was done was by
"cloning," whereby foreign DNA was inserted into a growing organism that was
"tricked" into synthesizing the cloned DNA along with its own. Another way
that DNA was reproduced was by the polymerase chain reaction (PCR). PCR re-
sults in the in vitro synthesis of large segments of a target DNA sequence, a tech-
nique utilized in research and clinical laboratories.
Mapping of the genome involved locating and identifying the genes present
within a strand of DNA (gene sequencing). The map facilitates the location
of genes that segregate with specific disease states. After mapping was com-
pleted, the next step was to determine the base sequence of each of the ordered
DNA fragments. Sequencing DNA was a long and excruciatingly difficult task.
In the mid-1970s Frederick Sanger, a molecular biologist at the Medical Re-
search Council Laboratory of Molecular Biology in Cambridge, England, de-
vised an elegant sequencing method that won him a second Nobel Prize in
Chemistry.
The HGP Mapping Project consisted of two major componentsthe Re-
source Center and the Directed Programme of Research. The first component,
the Resource Center, acted as a national repository and site for systematic work,
as well as distributary and reference center for human-mouse cDNA libraries,
yeast artificial chromosomes (YAC), DNA probes, computer facilities, and rele-
vant databases. In addition to the production of cDNA libraries and sequencing
of new cDNAs, work at the center included nonradioactive sequencing, hy-
bridization screening, polymerase chain reaction screening, oligonucleotide syn-
thesis, and in situ hybridization.
The second component, the Directed Programme of Research, served to ex-
pand work in various university departments and other institutions. In addition,
it supported research in three broad areas: general mapping of interesting ge-
nomic regions, evaluation and design of enabling methodologies and equipment,
and study of model organism genomes such as the mouse and the roundworm
Caenorhabditis elegans.
Currently, the speed with which disease genes are being identified continues
to increase rapidly because of improved genetic and physical maps. By intro-
ducing detailed human genetic mapping techniques, human genes have been
identified more rapidly. For example, Duchenne and Becker identified muscular
4 B
THE BDDK DF LIFE
dystrophy genes in 1986, entering a new era of medical treatment and diagnosis.
Also, construction of an E. coli clone library was started to analyze the E. coli
genome, and in 1988 the DNA polymerase chain reaction (PCR) was intro-
duced.
Three types of maps were used in the HGPgenetic, cytogenetic, and phys-
ical. The genetic map (genetic linkage map) consisted of thousands of landmarks
that were short distinctive pieces of DNA, more or less evenly spaced along the
chromosomes. Genetic maps had many uses, including identification of certain
genes associated with genetic diseases. Genetic maps enabled researchers to
identify an inherited disease by pinpointing the exact chromosomal location
of important disease genes in diseases such as sickle-cell anemia and cystic fi-
brosis.
The second type of map, physical maps, consisted of overlapping pieces of
DNA spanning an entire chromosome. Physical maps were used to isolate and
characterize individual genes and other DNA regions of interest. Physical maps
consist of ordered landmarks at known distances from one another, much like a
travel map indicating distances between cities along a highway. A physical map
represented actual locations (as compared with relative locations on a genetic
map) of identifiable landmarks. The completed physical map simplified the gene-
tic analysis of human disease.
The third type of map, cytogenetic maps, represented the appearance of a
chromosome when examined microscopically. These maps served to identify
specific chromosomes and chromosomal regions.
33
'
34
Currently, gene sequencing
involves taking DNA from human chromosomes, which is shredded into short
segments. These are fed into an automated machine that reads each biochemical
"letter" on the segment. Once the segments have been read, a computer puts
them together by assemblyfinding overlaps and matching adjacent pieces. This
is complicated by the fact that similar sequences occur many times in many
places. The final step involves annotation. This involves pinpointing the genes
along the chromosomes. These genes make up about 3 percent of the genome.
Once these are identified, researchers can figure out which ones make proteins
that cause disease or protect health. Understanding how and when genes make
proteins will give doctors new ways of looking at disease and lead to new treat-
ment.
Results and Surprises
Venter and his company, Celera, and Collins and the HGP team used different
strategies and methods to complete sequencing the human genome. Venter used
the whole-genome shotgun approach, whereas Collins and his HGP team used
landmark mapping and sequencing. Importantly, both teams reached the goals
that were set.
In completing the HGP, there were three primary surprises: first, scientists
found that the human genome has only about one-third as many genesabout
20,000 to 25,000 genes, rather than 100,000as originally thought. Interestingly,
this is about the same (20,000) as a nematode worm' s (Caenorhabditis elegans) or a
4 9
THE GENETI CS REVDLUTI DN
fruit fly's (Drosophila melanogaster) 14,000 genes. Surprisingly, in terms of genes,
humans appear only five times as complex as the bacterium Pseudomonas aerugi-
nosa. Interestingly, the 20,000 to 25,000 genes present about 90,000 or more dis-
tinct proteins encoded by the human genome. Genes build proteins to meet the
demands of each of the body' s 100 trillion cells.
Yet, despite its apparently light load of genes, the human genome is large.
Much of the human DNA does not contain human genes but rather is packed
with remnants of snippets of ancient DNA that have replicated and inserted
themselves into the genome many times over. This accounts for large chunks of
duplicated sequences called junk DNA. The sequence tells us that we received
more than 200 genes as gifts from bacteria that somehow infected a distant ances-
tor of ours and transferred some DNA.
Second, scientists discovered that proteins, the most complex large mole-
cules in nature, are much more complicated in humans than in animals or plants
and that each gene makes two or three proteins, not one as originally thought.
This is highly significant since it renders the one gene, one protein theory obsolete, at
least in humans.
Third, foreign DNA, derived from ancient microbial invaders, also populates
large portions of the human genome. This is significant because it implies that
humans share with bacteria some genes that regulate important processes such as
metabolic functions or enzyme creation. The typical human gene likely has twice
as many proteins as worm genes, giving the human cell an ability to build any
kind of protein the cell might need. However, humans use them differently than
do lower organisms. These protein domains have survived millions of years of
evolution.
35
From the HGP work, two lines of evolution converged on humans. The first
implies that one set of genes came from the first bacteria capable of living in an
oxygen-rich atmosphere. The second set came from the single-celled organisms
that gobbled up the bacteria and co-opted their ability to t urn oxygen into en-
ergy. Interestingly, genes from those bacteria still live in the human genome,
demonstrating the fusion of two different lines of evolution into the same
genome.
It was shown that hundreds of human genes appeared to have come from
bacteria millions of years ago. Whet her the bacteria infected humans or were car-
ried by a virus is not currently known. Perhaps the most intriguing question to
emerge from these analyses is this: How do relatively few genes build and main-
tain an organism as complex as a human, with 90,000 to 300,000 proteins and
100 trillion highly specialized cells?
The HGP has shown that genetic information is not evenly divided on the
chromosomes. Eric Lander of the Whitehead Institute Center for Genomic
Research in Cambridge, Massachusetts, a lead researcher for the HGP, best de-
scribed the genome as a "remarkably uneven landscape . . . Some chromo-
somes are chockablock with genes, [and] others are virtually devoid of genes.
The weirdest chromosome in the genome is [number] 19. It' s chockablock full
of genes and other functional elements, far beyond what you' d expect, given its
measly size. It's a mighty little chromosome there. Given its size, it has grand
aspirations. In contrast, chromosomes 4 and 8 barely pull their weight."
36
5 D
THE BDDK
Impact of the Human Genome Project
Completion of the HGP was a historic moment. No one will argue that mapping
and sequencing the human genome, whatever method used, has provided us with
useful, if not stunning, information. Leading to new drugs, new ways to prevent
or treat many illnesses, and better forecasts of peoples' lives, the information gen-
erated by the HGP promises to be the source book in the twenty-first century, if
not the third millennium. "Humanity has been given a great gift. With the com-
pletion of the human genome sequence, we have received a powerful tool for un-
locking the secrets of our genetic heritage and for finding our place among the
other participants in the adventure of life."
37
The HGP has already begun to revolutionize the practice of biomedicine.
Maps and sequences have aided scientists in finding genes, and thousands of
known inherited disorders have been identified as a result of the HGP. Today, the
HGP serves as a guide for scientists who are trying to find cures for diseases such
as Parkinson's, Alzheimer's, multiple sclerosis, muscular dystrophy, diabetes and
other diseases that afflict millions. Use of the HGP will enable scientists to find
other genes involved in various other genetic diseases.
Whereas mapping the human genome has increased our ability to under-
stand and eventually prevent or cure diseases, it has also allowed scientists and
others to develop techniques and instruments for rapid determination of gene
sequences on DNA. For example, Eugene Chan, who received U.S. Patent
6,355,420 for what he calls the "Gene Engine," has invented a machine that deci-
phers the human genome in less than thirty minutes. Chan says his new machine
takes genetic information, unwinds the information at extremely high speeds,
and reads it at even higher speeds. The machine has a chip that allows the user to
manipulate and control DNA at a very small scale. The chip has fluid channels in-
side it that stretch out the DNA and then read it with an amazing optical technol-
ogy. Chan' s machine has many uses. For example, when an individual is born, his
or her genome can be scanned, analyzed, and stored and the information reac-
cessed later.
38
With such stunning successes, scientists and clinicians have been given a pow-
erful resource that allows them to study and treat humans in exceedingly more
beneficial and sophisticated ways. In addition to its impact on biomedicine, the
HGP has had a large impact on industrial activities in society in producing vac-
cines, interferon, and other useful pharmaceuticals. Researchers are now able to
identify individuals predisposed to particular diseases and to devise novel thera-
peutic regimens based on new classes of drugs, immunotherapy techniques,
avoidance of environmental conditions that may trigger disease, and possible re-
placement of defective genes through gene therapy.
In April 2003 President George W. Bush issued the following statement upon
completion of the HGP: "The HGP provides us with the fundamental platform
for understanding ourselves from which revolutionary progress will be made in
biomedical sciences and in the health and welfare of humankind."
39
The ability to compare complete genomic sequences also has enabled scien-
tists to compare humans, worms, flies, and bacteria and has shown the common-
ality of life. Demonstrating obvious distinct differences, the HGP has provided
THE GENETI CS REVOLUTI ON
researchers with the capacity to solve the mysteries of human development and
evolution.
In a 2005 experiment, Purdue University molecular biologists challenged a
scientific law of inheritance that stood for 150 years. The scientists believe that
plants sometimes select better bits of DNA in order to develop normally even
when they inherited genetic flaws from their predecessors. Researchers found
that a plant belonging to Arabidopsis thaliana, a member of the mustard and wa-
tercress family, sometimes corrected the genetic code it inherited from its flawed
parents and grew normally like its unflawed grandparents and other ancestors.
The discovery leads scientists to wonder whether humans may also have the po-
tential to avoid genetic flaws or even repair them, proving that inheritance can
happen more flexibly than previously thought.
The conclusion by the Purdue scientists contradicts some basic rules of plant
evolution believed to be absolute since the mid-1880s when Austrian monk Gre-
gor Mendel proved that traits are passed on from one generation to another.
Mendel' s work earned him the title "Father of Genetics." Some scientists de-
scribed the results of the Purdue experiment as "spectacular" because it reveals a
novel way in which the genome can heal itself.
5 2
PART II
Beauty and the Beast
The birth in England of Louise Brown, the world' s first test-tube (in vitro fertil-
ization) baby, marked a revolution in fertility treatment. In spite of the reproduc-
tive miracle, however, there existed in the minds of many a certain apprehension
that the miracle of test-tube tots indicated the arrival of Aldous Huxley's un-
orthodox science. As a result, the conservative British government commis-
sioned Dame Mary Warnock of Cambridge University to form the Committee
of Inquiry into Human Fertilization and Embryology. The committee issued
sixty-four official recommendations.
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4
LABDRATDRY BABIES
New Biology, Old Morality
The in vitro fertilization controversy divided physicians and re-
searchers who were t orn between the lure of a new dawn of
knowledge as depicted in Brave New World and the safety of a tra-
ditional code of ethics.
Dame Mary Warnock, Girton College,
Cambridge University
The creation and birth of the world' s first in vitro fertilization (IVF, "test tube")
baby was far from being an ordinary event. Its occurrence made headlines
throughout the world because it was a new way of beginning life. However, be-
hind the beauty of IVF there lurked a beast in the form of nightmares and con-
cerns voiced by theologians, ethicists, lawyers, and philosophers who, on both
sides of the Atlantic, warned that the medical miracle of IVF indicated the arrival
of unort hodox medicine as forecast in 1932 by Aldous Huxley in his novel, Brave
New World.
Huxley's Brave New World
In Huxley's Brave New World, students tour the fictitious Central London Hatch-
ery and Conditioning Centre where they observe various machines and tech-
niques that promote the production and conditioning of embryos. Absent are
fathers and mothers in the usual sense and family and marriage are nonexistent.
Surrogate parental relationships with children are filthy and improper and feelings
are obsolete. Overall, the book represents a society without moral controlsone
THE GENETI CS REVDLUTI DN
where only carnal pleasures are pursued, and where any rituals are orgiastic in na-
ture. While on the tour in Brave New World, students learn that the key to social
control is the "Bokanovsky Process" in which a single human egg (ovum) could
produce up to ninety-six identical twins, each mentally and physically identical to
all others and all capable of contributing to a social stability.
Although written more than seven decades ago, many of the technologies de-
scribed in Brave New World have, at least in part, become realities. Huxley did not
intend to evoke just how wonderful our lives could be if the human genome were
rewritten, yet early in the twenty-first century we have already experienced in
vitro fertilization and other assisted reproductive technologies, recombinant
DNA technology (genetic engineering), mood-altering drugs, stem-cell research,
and reproductive and therapeutic clonings, and have seen completion of the hu-
man genome project (HGP).
The Road to Oxford
Huxley's Brave New World brought back memories. Leaving my home on the
Nort h Dakota prairies early one mid-July morning in 1985,1 boarded a jet to Min-
neapolis, where I embarked on a direct flight into London' s Gatwick airport. From
there, I proceeded by bus directly into the city of Oxford where I resided for sev-
eral weeks at the Queen' s College at Oxford University. A Bush Foundation (St.
Paul, Minnesota) faculty development grant had enabled me to participate in an
international science seminar, Medicine, Ethics, and Society, held at the Queen' s
College.
Oxford is a university traditionally renowned for study of the arts and one of
the world' s great scientific universities as well. Each of the forty colleges com-
prising Oxford University has its famous alumni. The Queen' s College, one of
Oxford' s oldest colleges, was founded in 1340 by Robert of Eglesfield, chaplain
to Queen Philippa, wife of King Edward III. Like other Oxford University col-
leges, the Queen' s College boasts of the famous pupils who once attended. John
Wyclif, the English religious reformer and first translator of the Bible into En-
glish, attended during the years 1363-65 and 1374-81. King Henry V studied at
Queen' s while he was Prince of Wales prior to becoming King of England. Dur-
ing the seventeenth century, the noted playwright Wycherley attended, as did
Edmund Halley, the Astronomer Royal after whom Halley's Comet is named.
World-renowned philosopher Jeremy Bentham was an undergraduate in 1760,
and during the nineteenth century the art critic Walter Pater was a student.
An International Forum
Attracting some of the world' s greatest philosophers and ethicists, the interna-
tional forum Medicine, Ethics, and Society was attended by over one hundred
persons representing seventeen countries and was designed to discuss social,
moral, and ethical ramifications stemming from scientific breakthroughs in biology
and medicine.
5 6
LABDRATDRY BABI ES
The forum's key-note speaker, Dame Mary Warnock, Mistress of Girton Col-
lege at Cambridge University and Senior Research Fellow, St. Hugh' s College at
Oxford University, addressed seminar participants in the spacious Examination
Room of the Queen' s College. Warnock told forum scholars that she had been
commissioned by the conservative British government's Department of Health
and Social Security to form a committee to conduct inquiry into human fertiliza-
tion and embryology and to make recommendations. Need for the study, Warnock
reported, evolved after the creation and birth of the world's first "test tube baby,"
Louise Brownconceived and born in England. Warnock' s committee was estab-
lished in 1982 to examine the social, ethical, and legal implications of recent and
potential developments in the field of human assisted reproduction.
Warnock told forum scholars that when scientists first suggested that IVF
might be applied in the treatment of infertile women, a heated debate arose in the
United States (and to a lesser degree in the United Kingdom) about whether it
was moral to use IVF technology with the intent to create a human baby: "For de-
cades an intense IVF controversy divided physicians and researchers who were
torn between the lure of a new dawn of knowledge as depicted in Brave New
World and the safety of a traditional code of ethics."
1
As a result, for decades philosophers, theologians, ethicists, and lawyers on
both sides of the Atlantic debated the morality of IVF, a technology centered
mainly around promises, trust, and commitments.
2
In July 1984 the Warnock
Committee issued its detailed report, Report of the Committee of Inquiry into Hu-
man Fertilization and Embryology in the United Kingdom.
3
The report addressed
topics of in vitro fertilization, surrogacy, the freezing and storage of reproductive
materials, and the use of embryos for research. Considered a crucial text in the
discourse on assisted reproductive technologies, the study was considered a point
of reference to countries including the United States, Great Britain, Denmark,
Germany, and France.
The World's First "Test Tube Baby"
Born July 25, 1978, in Oldham, England, Louise Brown was a healthy five-pound,
twelve-ounce baby girl, the first ever conceived outside a mother' s body under
controlled laboratory conditions. The IVF procedure was deemed necessary
since Louise's mother had an inoperable blockage of the fallopian tubes which
prevented her from getting pregnant in the usual way.
The egg that produced Louise Brown was fertilized in vitro via embryo trans-
fer, a process whereby an egg is taken from the mother' s body, fertilized by the
father's sperm, allowed to grow to embryo stage in the laboratory, and returned
to the mother' s uterus for further development. The merger of an egg and sperm
is technically called a "zygote" and contains the full set of forty-six human chro-
mosomes, twenty-three from the egg and twenty-three from the sperm.
Today, more than twenty-five years after the birth of Louise Brown, IVF con-
ceptions in a petri dish from a mother' s egg and a father's sperm seem relatively
natural. More than one million test tube (IVF) babies have been conceived and
born healthy, and the debate now is nearly nonexistent. Governments all over the
5 7
THE GENETI CS REVDLUTI DN
world have since adopted policies that allow the regulated use of IVF on the
proven assumption that it produces more good than harm.
Drs. Edwards and Steptoe
The British medical researchers who performed the first IVF procedure that cre-
ated Louise Brown were Drs. Robert Edwards and Patrick Steptoe, who took it as
their duty to satisfy the natural desire of every couple to have a child, by natural
or artificial means. Edwards and Steptoe' s partnership began in 1968 at the Cen-
tre for Human Reproduction in Oldham, England, where Edwards had succeeded
in fertilizing the first human ova outside the womb. Over time this technology
resulted in the births of thousands of IVF babies, including Louise Brown and
her younger sister.
4
Dr. Robert Geoffrey Edwards, born September 27, 1925, attended the Uni-
versities of Wales and Edinburgh, served in the British Army (1944-48) and
worked as a physiologist and medical researcher at various universities in Britain
and the United States. He began his work on the human egg in 1963 and his first
paper on the subject was published in 1965 in the prestigious scientific journal
Lancet.
5
Dr. Patrick Christopher Steptoe was born on June 9, 1913, in Winey, Oxford-
shire, England. He died on March 21, 1988, in Canterbury, Kent, the day before
he was to be made a Commander of the Order of the British Empire. In 1939,
Steptoe graduated from the University of London' s St. George Hospital Medical
School and joined the Royal Navy Volunteer Reserve, serving as a surgeon until
his ship was sunk and he was taken prisoner and held by the Italians (1941-43).
After his release, he continued his medical training in London, Dublin, and Man-
chester before becoming senior obstetrician and gynecologist at Oldham Hospi-
tals (1951-78). While at Oldham, Steptoe conducted research on sterilization and
infertility and published Laparoscopy in Qynecology (1967), concerning the use of
the laparoscope, a narrow tube with a built-in fibre light. Edwards and Steptoe' s
first joint paper was published in 1970.
6
A Huge Impact
The birth of Louise Brown had a huge impact on the ethical and moral debate
surrounding the use of IVF. Overall, there was a sense of pride in the technolog-
ical achievement, as well as relief of anxiety for couples who were infertile. Yet,
for some there was an uneasiness with a technique that presented an uncontrolled
scientific advancementone capable of manipulation. In describing IVF's rapid
advancement, Warnock said: "There was a sense that events were moving too fast
for their implications to be assimilated."
7
Other concerns arose, primarily over moral and ethical questions involving
the possible creation and destruction of human beings, the normality of the off-
spring, a change in the natural patterns of human reproduction, and the potential
for future genetic engineering in our species.
5 B
LABDRATDRY BABI ES
Responses of people to IVF fell into three general categories. First, for many
the anathema response existedthe entire innovation of laboratory procreation
was morally unthinkable. Simply, science had become a beast that had gone too
far! People had visions of moving assembling lines of test tubes and petri dishes
in the biological laboratory where embryos were made and discarded by imper-
sonal laboratory workers in full factory-like connotation, much like Brave New
World. To those experiencing this kind of response, IVF represented a complete
depersonalization of marriage and parenthood.
Second, to those experiencing an assimilation response the goal was an ancient
onefor childless couples to have children. Neither the ends nor the means in-
volved in creating a test tube baby was a drastic departure. At the center of the re-
sponse were questions such as: When is a human being a human being? Does life
begin at conception when the egg and sperm unite? Is there valid scientific evi-
dence when actual human life exists?
Third, those who experienced an apprehension response believed that there were
many things that happen to humans in life that are not welcome. Persons experi-
ence a pronounced uncertainty, one that is often poorly tolerated. In spite of these
fears, by the 1980s several groups, including Carol Wood' s group in Australia, were
experimenting with human IVF and announcing more IVF pregnancies.
Others believed IVF was unethical because it violated the sanctity of mar-
riage and a proper family environment for child bearing. Still others argued that
although sexual intercourse might well be an act of love that sanctified marriage,
it did not guarantee a happy family environment. Proponents of the new technol-
ogy argued that IVF demanded sacrifice on the part of both male and female
partners far beyond anything required for normal procreation.
Another concern of opponents of IVF was that the technology entailed un-
known risks to potential children who could not give consent. Proponents of
IVF believed that it was unlikely that the risks involved with IVF were substan-
tially greater than they were with normal fertilization. Others believed that IVF
was unethical because the technique made possible wholesale reconstructions of
the human body. Opponents of IVF believed that IVF was unethical because sci-
ence does not have the right to manipulate nature, whereas proponents argued
that if it was ethically acceptable to seek medical care for a reproductive disorder,
it was ethically acceptable to seek care that required IVF.
When the wide-spread IVF controversy initially began, opponents of IVF
were concerned that it was unethical because the risks of publicity to a child so
conceived would not allow the normal development of the child. That idea is
now known to be false, based on the normal development of Louise Brown and
her sister, as well as thousands of other IVF babies. Louise Brown currently
works as a postal employee and lives in Bristol, England. Because IVF has gained
wide acceptance throughout the world, undue publicity is currently minimal.
Infertility: "Genetic Death"
It is not difficult to imagine infertility, sometimes labeled "genetic death," as
causing great anxiety to many couples, thus putting a strain on their marriage. As
5 9
THE GENETI CS REVDLUTI DN
powerful as the innate will to survive, the desire to have children is one of hu-
manity' s strongest urges, symbolizing a human' s attempt to achieve immortality
and leave something of him or herself to posterity. Understandably, then, the de-
sire of an infertile couple to seek help in creating their own children is also very
powerful. One out of every six couples struggles to become parents. However, in-
fertility is not confined to those who are married, but single women and men,
widows and widowers, and homosexuals and lesbians, as well.
For over a century, physicians have offered the practice of donor insemina-
tion as a means of providing children to infertile couples. Yet, despite greatly in-
creased abilities to diagnose and treat the causes of infertility, many couples still
remain involuntarily childless. It is not surprising, then, that IVF was a consider-
able breakthrough that opened new doors for the alleviation of infertility and the
science of embryology.
At the time of the IVF breakthrough, there were those who asked: Why
would anyone want to make babies via IVF? The answer is that, in many instances,
the "natural" method is not possible. Infertility is an enormous problem world-
wide and is not constrained by a high birth rate or an overpopulated nation.
8
The dramatic increase in the incidence of infertility over the last five decades
has been attributed to a number of factors, including an increase in the incidence
of venereal diseases that destroy the reproductive apparatus of both men and
women. In addition, females are starting their families at a later age, when their
natural fertility has already begun to decline. Another major increase in infertility
has been attributed to the use and abuse of drugs and narcotics that play havoc
with spermatogenesis (formation of sperm) and oogenesis (formation of eggs).
The treatment of infertility has raised legal and ethical questions concerning
equity and justice, falling roughly into two broad categories: questions of social
justice and questions of individual justice.
9
In July 2002 it was announced that
fertility clinics were under pressure to review security procedures after a white
couple had black twins following an in vitro fertilization mix-up. The mix-up, it is
believed, was due to human error and was the first of its kind in Britain. The fer-
tility clinic, linked to a state-funded National Health Service hospital, somehow
confused sperm, eggs, or embryos belonging to a black couple with those from a
white couple. IVF experts say there were two main possibilities for the error: ei-
ther Mr. B's sperm was used by mistake to impregnate Mrs. A' s eggs, which were
then implanted in her; or that an embryo created using Mr. B's sperm and Mrs.
B's eggs was accidentally implanted in Mrs. A. Most experts believe the latter was
the more likely.
10
Donated Eggs
Infertility may be due to reasons other than blocked oviducts, and because of
this, successful donation of eggs is sometimes necessary. After superovulation is
induced, a mature egg is recovered from a fertile woman donor and is fertilized in
vitro, using the semen of the husband or male partner of the infertile woman.
Another technique uses a mature normal donated egg with one set of chromo-
somes (twenty-three; haploid). The chromosomes are sucked out of the egg and
6 D
LABDRATDRY BABI ES
the nucleus from a healthy body (somatic) cell with its forty-six chromosomes is
injected into the empty egg, producing an egg with two sets of chromosomes
(forty-six; diploid).
To make the egg viable for fertilization one set of chromosomes is removed
by shocking the egg electrically or injecting it with a chemical that pushes the ex-
tra set of chromosomes out. The mature egg is then ready for fertilization by a
sperm. The resulting embryo can be implanted in the same woman from which
the egg was obtained or donated to another woman (a gestational mother). If the
embryo implants, the woman may carry the pregnancy to term.
Donated Sperm
Sperm cryopreservation and sperm banking also have become a widely accepted
part of our culture, and sophisticated procedures and techniques are available. As
early as the 1940s cattle breeders and veterinarians used the process of cryop-
reservation of bull semen and artificially inseminating heifers. However, it wasn't
until the 1950s that the methods for cryopreserving human semen and artificial
insemination were refined, resulting in the first human birth. One of the first hu-
man sperm banks was started in the early 1980s.
Today, sperm banks are commonplace and it has been experimentally shown
that sperm motility, viability, and morphology are not affected by proper long-
term preservation over many years. Sophisticated methods and techniques are
currently available for freezing and storing human semen.
Many reasons are given for men freezing and storing their semen. Those in
high-risk occupations, as well as sports figures, at times elect to protect their fu-
ture against possible injury that could affect their reproductivity. Vasectomy pa-
tients sometimes store their sperm prior to their procedure in case they may
someday choose to father another child. Because surgery, chemotherapy, and ra-
diation may render male patients who are undergoing cancer treatments sterile,
many males opt to store sperm prior to these procedures.
In September 2002 it was announced that U.S. and British scientists had put
together a genetic profile ("fingerprint") of healthy sperm. Heralded as a major
step in the understanding, diagnosis, and treatment of male infertility, the genetic
"fingerprint" provides a necessary molecular "benchmark" against which to
compare men with fertility problems. The profile is also useful in fertilizing eggs
and in early embryo development.
11
A recent spectacular achievement was an off-
shoot of IVF called intracytoplasmic sperm injection. A single sperm is injected
directly into the egg. This is particularly useful when the quality and number of
sperm are low.
Surrogacy
Surrogacy is the practice whereby one female carries a child for another with the
understanding that the child will be handed over after birth. At times, surrogacy
becomes necessary for the alleviation of infertility and is frequently used among
6 l
THE GENETI CS REVDLUTI DN
women with uterine abnormalities that preclude normal pregnancy Surrogacy is
also used by women who wish to hire gestational mothers in order to avoid inter-
ference with their careers or sports activities.
Who are the women willing to be surrogates? Often, child bearers are poor
women who are willing to be surrogate mothers for good pay. However, even
though money is an important motive for many surrogate mothers, for many it is
not the primary motive. Other reasons given by surrogates include the love of
children and the gratification offered by the children, empathy with the infertile
female (a thoughtful act of generosity on the part of one woman to another), and
the drive to generate parenthood for others.
The contribution of the surrogate mother is great, intimate, and deeply per-
sonal. Many women believe that surrogacy is a feeling of self-actualization. This
is especially true in cases where one female relative carries the pregnancy for an-
other. For these couples, it offers them their only chance of having a child gene-
tically related to one of them and may be the only way that the husband of an
infertile woman can have a child.
In the case of a relative gestating another' s baby, certain questions surface:
Whose child is he or she? Is the female morally justified in gestating another' s
child? How does the rest of the family feel about her giving birth for a relative?
Will other members of the family feel obligated to perform the same act of kind-
ness?
Psychological and legal consequences in surrogate motherhood may be sig-
nificant. Opponents of surrogacy believe that it is an attack on the marital rela-
tionship between couples because a third party is introduced into the process of
procreation. Others believe that surrogacy is degrading because poor women are
used by rich women to have their babies in order to avoid the discomfort of preg-
nancy. Opponents view surrogacy as inconsistent with human dignity and believe
that a woman should never use her womb for financial profit.
Others view surrogacy as buying and selling of human flesh, a process that is
dehumanizing. Many believe surrogacy should be prohibited. Opponents believe
that surrogacy is harmful to a child's future self-esteem because the child will
have been purchased for money. Others feel that surrogacy distorts the relation-
ship between mother and child because the woman allows herself to become
pregnant, carries the child nine months, and then gives it up. As a result, the
bonds of the child are with the carrying mother and the separation is damaging to
the child.
In the first known case in the United States in which a woman was paid to be
a surrogate, a child was born in November 1980 to a thirty-eight-year-old
mother of three children. Rather than using her real name, she used a pseudo-
nym, Elizabeth Kane. For an undisclosed amount (reported to be between
$5,000 and $10,000), Kane permitted herself to be artificially inseminated with
the sperm of a man from Louisville, Kentucky, whose wife was infertile. Kane
signed a formal agreement, releasing her parental rights to the baby. The parents-
to-be were present at the birth of the healthy eight-pound, ten-ounce baby boy.
Kane asked and received the couple' s permission to briefly hold the baby and
then handed him over to the parents, the baby's genetic father and his adoptive
mother.
6 2
LABDRATDRY BABIES
In a later case, Mary Beth Whitehead, a twenty-nine-year-old homemaker
from New Jersey, signed a contract paying her $10,000 to bear a child for Eliza-
beth and William Stern. Elizabeth Stern was infertile and the couple desperately
wanted a baby. Whitehead allowed herself to be impregnated by the sperm of
William Stern and agreed to carry the baby to term and to turn it over to the cou-
ple in return for the money.
However, near the birth of the baby, Whitehead changed her mind and de-
cided to back out of the legal agreement with the Sterns. The Sterns refused to let
Whitehead out of the agreement and hired Noel Keane, a Dearborn, Michigan, at-
torney who owned and operated the first surrogacy agency. Keane, on behalf of
the Sterns, demanded that Whitehead turn the baby over to them after it was born
and give up custody to it. The litigation, known as the "Baby M" case, was heard
in room 217 of the Bergen County Courthouse in Hackensack, New Jersey. The
case captured national attention, mainly because it challenged traditional defini-
tions of parenthood and tested the adaptability of the law to radical social change.
At the time of the adoption, the six-page document that Whitehead and
William Stern had signed placed them in a gray area of the law. Consequently, the
judge ruled that Whitehead, as the surrogate mother, had to turn the baby over to
the Sterns who had contracted her to carry the child because she had to "honor
the contract" she signed with the couple. However, an appeal to a higher court re-
instated some of Whitehead' s parental visitation rights to see the child.
When Does Human Life Begin?
At the heart of the IVF controversy is the question: When does human life be-
gin? Some believe that life begins at conception, when an egg is fertilized by a
sperm, whereas others believe that life is a developing process, coming into being
only when the resulting mass of cells begins to appear human.
Those who believe that life begins at conception say that what exists before
conception is not life. They argue that since the sperm and the egg are sex cells
(haploid cells, each containing twenty-three chromosomes), by themselves they do
not constitute human life. Rather, they can become whole only when they unite
to form the fertilized egg called the zygote (a diploid cell containing forty-six
chromosomes). From the time of fertilization by the sperm, the egg takes on an
entirely different destiny. The genotype conferred at conception does not merely
start life, it defines life. From a biological point of view, life begins at conception,
and the destruction of a fertilized egg or embryo constitutes the destruction of a
human life.
Others believe that life is a continuous process of development, beginning
with a molecular thread of DNA, the "essence" of life and the basic material that
forms the building blocks of life, the genes and the chromosomes. Those who be-
lieve this theory state that life begins well before conception and extends long af-
terwards. They believe that the egg and the sperm, each with its own genome of
twenty-three chromosomes, are very much alive.
Under normal conditions, fertilization of the egg by the sperm may not result
in a person but rather into a cell mass that ultimately divides into two major
6 3
THE GENETI CS REVDLUTI DN
components, the embryoblast and the trophoblast. The embryoblast becomes
the fetus, and the trophoblast becomes the placenta, the umbilical cord, and the
extraembryonic membranes. Some believe that the trophoblastic derivatives are
alive and human, with the same genetic composition as the fetus. Since they are
discarded at birth, many wonder whether they deserve the same moral standing
as a fully developed human. Many argue that human embryos are biologically
alive, even at the blastocyst stage (the blastocyst is the largest embryo and is
barely visible to the naked eye). Others believe that the embryo, if not a human,
is potentially a human, as are the egg and the sperm.
Years ago, theologians particularized the human desire to identify person-
ness. Many question when "ensoulment"the moment when the soul (appar-
ently a quality not shared by other species)enters the embryo. Does it occur at
conception, at implantation, at quickening, or at birth? There are those who
claim that laboratory reproduction, such as in vitro fertilization, is no longer hu-
man reproduction and may be ethically correct only when the normal process of
birth cannot take place.
Embryo Loss
There has been considerable concern over embryo loss in females. Because in
vitro fertilization is the deliberate creation of embryos, the most frequently
voiced concern is that IVF is unethical because embryos are destroyed in the pro-
cess or after transfer to the uterus, or that embryos that are not transferred are
somehow destroyed. In creating Louise Brown, it was originally reported that
Edwards and Steptoe transferred over 100 embryos before their first success.
12
What happened to the excess embryos?
Various pro-life groups believe that as horrible as it may be to discard em-
bryos, it is far worse to perpetuate them in their laboratory existence. Numerous
questions arise during the IVF process: What happens to the embryos that are
discarded at the end of the day? Are they washed down the sink? Does this
amount to abortion or murder? Who decides the grounds to discard embryos?
Are discarded embryos considered fit material for experimentation? Should they
be donated to those who wish to have the otherwise unwanted embryo? Whose
embryos are they? The woman's? The couple's? The geneticist's? The obstetri-
cian's? Who will the children be, and who will be their parents? What is their so-
cial definition?
Some argue that embryo loss is not unusualthat there is a high rate of em-
bryonic loss that occurs in women during the normal reproductive process.
13
They cite a similar phenomenon has been known for many years to occur nor-
mally in non-primates such as rabbits and pigs, and other mammals as well.
14
'
15
Over a half-century ago, embryonic loss in women was recognized and it was ob-
served that potentially abortive ova could be recovered from women who were
considered to be normally fertile.
16
Biggers estimated embryo wastage and con-
cluded that by the time pregnancy was recognizable, half the embryos had been
lost. With the IVF procedure, he determined, a larger proportion of the embryos
was lost by the time a pregnancy was recognizable. Further, Biggers concluded
6 4
LABDRATDRY BABIES
that during the remainder of pregnancy, another quarter of the embryos perished
and were aborted.
17
Pro-abortionists at times argue that even a significant number of fertilized
eggs (zygotes) fail to implant and therefore do not result in pregnancy. They use
this as "evidence" that even Mother Nature does not consider the fertilized egg
genuine human life, any more than she does the hundreds of thousands of eggs
and millions of sperm that are wasted.
Human Embryo Research Panel
The subject of human embryo research has been highly controversial. In December
1994 the National Institutes of Health (NIH) appointed the Human Embryo Re-
search Panel to make recommendations regarding human embryo research and to
offer ethics-based advice on how the NIH should research the human embryo. The
panel responded by trying to prove that the embryo' s moral status is greater than
that of other human tissue but less than that of a baby. In doing so, they hoped to
convince officials that respect must be granted embryos as early human life, but not
at the expense of promising research for the benefit of public health.
The panel concluded that women should not be paid for donating eggs for re-
search, although payment for egg donation to private fertility clinics could con-
tinue. The panel also proposed a ban to prevent the commodification of embryos
and the exploitation of women. The ban, however, foreclosed a choice for women
and had significant effects on the availability of eggs for researchers.
The panel tried to prevent the development of a two-tier market for eggs
eggs from wealthy women in contrast to eggs from low-income women. Most of-
ten, eggs intended for fertility clinics were acquired from high-income women
and usually had greater value in the market than eggs acquired for research pur-
poses that were provided by poor women or women of color.
The panel had a significant degree of concern for researchers in two areas.
First, it recommended that researchers be allowed to continue to use preexisting
embryos from fertility clinics despite the fact that donors were paid for these em-
bryos. Second, the panel concluded that the profit motive was acceptable for re-
searchers as long as subjects in federally funded embryo experimental protocols
were informed of the financial interest of the researcher as part of the consent
process.
Sperm, Eggs, and Embryos as Property
As developments in reproductive technology advanced, new and difficult moral
and ethical questions intensified and were presented to courts as legal issues of
first impression. As a result, judges had to decide the law at the frontier of repro-
ductive technology.
The possibility of posthumous reproduction with preserved sperm was one
such dilemma facing the courts. In the unique case of Hecht vs. Superior Court, the
children of William Kane fought with Kane's lover over possession of sperm that
6 5
THE GENETI CS REVDLUTI DN
Kane had deposited in a sperm bank. Kane had signed a legal document that
Hecht, his girlfriend, could use the sperm to conceive children after he commit-
ted suicide. As a result, the court was faced with the unique question of whether
sperm could be treated as property and whether sperm could be left to another
by execution of a will. The analysis proceeded in three main parts.
First, legally, property rights exist whenever a person has the ability to sell or
transfer control of something. In order to answer the question of whether courts
should honor Kane's intent to transfer control of his sperm to Hecht, it became
necessary to address the moral issues of Kane's purposethe ethical problems of
posthumous reproduction.
Second, legal and moral arguments existed against allowing posthumous re-
production. Protection of unborn children from potential harm is an inadequate
basis for a morally based legal ban on posthumous reproduction.
Third, arguments existed against commodification of body parts and against
the commercialization of reproduction in particular. As a result, it was concluded
that the transfer of sperm using a will does not implicate the concerns that justify
opposition to commercial traffic in body parts and reproductive capacities.
Concerns for individual autonomy and privacy in matters of reproduction
justify the transfer of sperm by will. Various considerations arise. For example,
sperm can last a long time when frozen. It might take a widow years to decide
whether or not she wants to use the semen. In France, a court ruled that a man' s
sperm should be buried with him. These days, a greater number of families are
being asked whether they want to harvest the sperm from a son in a coma or a
husband who just died in an accident. Is this "cheating death" or is it more akin
to rape?
Consider the following hypothetical story with regard to unused embryos.
Jack and Sally of Philadelphia, Pennsylvania, were married for six years
before they decided to try to conceive a child. When they married,
both had wanted to have children. However, after trying for several
years unsuccessfully to have a child, the couple visited a fertility clinic
to obtain help. Sally was induced to produce several eggs, which were
fertilized by Jack's sperm. As a result of the fertilization, several eight-
cell embryos were artificially produced in vitro. Although Sally was im-
planted with the embryos several times, all attempts were unsuccessful.
Several years later Jack and Sally's marriage deteriorated and, de-
spite counseling, in the end they filed for divorce. At the time of di-
vorce, they had twelve frozen embryos stored at a Philadelphia fertility
clinic. Despite their divorce, Sally decided to keep the embryos for fu-
ture use in producing a baby. Jack, however, wanted to donate the em-
bryos to a private research company.
Both Jack and Sally had signed a consent form at the fertility clinic
that stated that any unused embryos would be donated to research.
However, the embryos could not be released without the consent of
both donors. The agreement stated that in case of divorce, ownership
of the embryos would be determined in a property settlement or de-
cided by a court of law.
6 6
LABDRATDRY BABI ES
In Britain there is a law that says unclaimed frozen embryos are to be kept
only five years. In the United States there are no such laws and few rules beyond
consent forms. At some IVF clinics the time limit on embryos extends to the
donor' s menopause.
Dramatic advances are occurring in reproductive science, particularly in cryo-
genic preservation of human sperm, eggs, and embryos. It is a time when courts
and legislatures increasingly are called upon to reconcile property interests of the
reproductive partners and their families and the rights of third parties. As clinical
procedures improve and more individuals and couples use in vitro fertilization,
cryogenic preservation, surrogacy, and single parent reproduction, traditional
property and proprietary issues need to be reconciled. In these and other cases,
reference to traditional property concepts will provide a valuable framework for
the merging public policy debate. If reproductive material such as sperm is prop-
erty, can this be left in wills? Would a child conceived posthumously share the es-
tate with existing heirs?
Ellen Goodman of the Washington Post Writers Group wrote the following:
Lately, I have tried to imagine introducing my late grandmother to the
5-year old twins. Grandma, I would say, meet Michayla and Mackenzie
Woodward. One of the girls has eyes just like her father. The other
looks like her dad around the chin and the mouth. Oh, by the way, the
girls were born two years after his death.
My grandmother' s attitude toward new reproductive technology
never went beyond her repeated wish: "One man should have one
baby!" How would she respond to this information from the frontier?
With her signature huff of skepticism? "Hoo ha."
For that matter, I would like to introduce the twins' mother Lau-
ren to the Massachusetts legislators of 1836. These men thought
they' d covered all bases, when they voted to allow a child born posthu-
mously to inherit a father's estate. Hey, guys, what about a child con-
ceived posthumously?
Posthumous conception? Postmortem creation? We live in a world
in which we can separate reproduction from sex. We have sperm and
eggs and embryos stored away in the freezers of myriad reproductive
clinics. And now we are learning that we can separate reproduction
from death.
The Woodward story was a mix of unplanned tragedy and planned
parenthood. When Lauren' s husband Warren was diagnosed with
leukemia and faced chemotherapy, he banked his sperm for a future
family. After Warren died at 30, Lauren created their family.
Lauren called her girls "a miracle" and won the right to have her
late husband called the father on their birth certificates. But when she
sued for survivor's benefits under Social Security, the federal courts
asked for a state ruling.
Last week they got it. The Massachusetts Supreme Judicial Court,
the highest court ruling so far on posthumous conception, said that
children can be the legal heirs of a dead parent as long as (1) they are
6 7
THE GENETI CS REVDLUTI DN
biologically related to the father and (2) he gave his consent both to
creating children and supporting them after his death.
"Posthumously conceived children may not come into the world
the way the majority of children do. But they are children nonethe-
less," wrote Chief Justice Margaret Marshall. When Woodward proves
her husband' s consent in a district court, this will be a closed case. But
a closed case with dozens of open ends.
I confess to mixed feelings about deliberately reproducing chil-
dren whose only relationship with a parent is through the genes. I was
appalled when a California man left 15 vials of frozen sperm to his girl-
friend before he committed suicide.
At the same time, I understand the impulse to "cheat death," as
another widow and mother once put it. I understand why some sol-
diers leave behind sperm when they go to war and some cancer pa-
tients store a family when they face death.
18
Questions and Answers; Lessons Learned
It is doubtful whether the general public, at the time of Louise Brown's birth, ap-
preciated the magnitude of the scientific achievement. Today it is quite different,
and IVF is recognized as one of the great medical breakthroughs of our time by
the general public and scientists alike.
Medicine and technology have grown together over the years to overcome
an obstacle of nature. Over a million test-tube babies have been conceived and
the once-heated debate over IVF has dwindled to almost nothing. The average
probability of an infertile couple taking home a baby after IVF is one in five,
about the same chance that healthy couples have of conceiving naturally each
menstrual cycle.
What was new when the IVF method was first introduced was that sexual in-
tercourse was no longer needed for generating new life. Rather, the new technol-
ogy provided the corollary to the pill: babies without sex. In retrospect, Louise
Brown's conception in a petri dish from her mother' s egg and her father's sperm
now seems relatively natural.
After Louise Brown's birth a utilitarian response dominated. No moral evils
were involved in IVF if all parties were freely consenting and there was a positive
balance of benefits over harms. Since that time, governments all over the world
have adopted policies that allow the regulated use of IVF on the proven assump-
tion that it produces more good than harm.
When IVF was first introduced, substantial moral issues in the new technol-
ogy centered around promises, trust, and commitments.
19
Pointed questions
were asked: When does human life begin? What is the value of the human em-
bryo? Do humans have inherent properties that make them valuable and if so,
when do they acquire these properties? What is the value of genetic reproduc-
tion? What are the human' s genetic and personal rights and duties? Is there a di-
rect connection between genetics and people with moral rights? Is geneticism, like
racism and sexism, a valid case for arguing societal relationships?
6 B
LABDRATDRY BABI ES
Other questions demanded answers: Whose right is it, a woman's or a couple's,
to procreate? Is it a right to carry and deliver (i.e., only a woman' s right) or is it a
right to nurture and rear? Is it a right to have your own biological child? Is the in-
ability to conceive considered a disease (if so, whose disease is it?) Does infertility
demand treatment wherever foundin women over seventy? In virgin girls? In
men? Can these persons claim either a natural desire or a natural right to have a
child, which the new technologies might or must provide them? Does infertility
demand treatment by any and all available meansby artificial insemination, IVF,
extracorporeal gestation, parthenogenesis, cloning, stem-cell research?
20
All human beings enjoy an unrestricted and fundamental right to procreative
liberty. There is support for such a claim in the U.S. Constitution, the Universal
Declaration of Human Rights of the United Nations, and declarations of human
rights issued by various other national and international organizations. Newer
technological methods for making babies require prevention of transmission of
inherited diseases such as cystic fibrosis or missing or defective chromosomes to
prospective children. Human embryo experimentation, whether it is utilizing em-
bryos left over from IVF or more recently, the technology to harvest stem cells
from human embryos, has serious moral and ethical implications that need to be
addressed in any discussion of such experimentation.
21
Advances in human biomedicine have opened new avenues and given hope to
many. Yet, an uncertainty exists whenever persons do not understand a situation
and cannot predict the outcome. Because few people tolerate uncertainty well, it is
important to remember that before we ask what a new medical technology will do
for us, we need to ask what it will do to us.
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5
THE WARNDCK REPORT
The task you set the Inquiry was not an easy one. The issues
raised reflect fundamental moral, and often religious, questions
which have taxed philosophers and others down the ages. Rightly,
you chose a membership which encompassed not only the many
professions with a concern in these matters but the many reli-
gious traditions within a society, so that as many viewpoints as
possible could be brought to bear on the morally sensitive issues
before us.
Dame Mary Warnock's June 26, 1984, letter to
the British government on behalf of the
Committee of Inquiry
The Committee of Inquiry into Human Fertilization and Embryology, also
known as the Warnock Committee and the Inquiry Committee, convened in July
1982 and was chaired by Dame Mary Warnock, philosopher and Mistress of Gir-
ton College of Cambridge University. The remaining fifteen members of the
committee included professionals in theology, medicine, natural science, social
science, law, and ethics.
Tasks of the Warnock Committee
The Warnock Committee was set up to examine, among other things, ethical im-
plications of new developments in assisted reproductive technologies. In Great
Britain, ethical committees such as the Warnock Committee were used to advise
THE GENETI CS REVDLUTI DN
governments, with a general intention to include a fair number of different points
of view.
1
Acknowledging that there was no such thing as a moral expert, the commit-
tee's task was primarily to give advice to British Ministers, based on moral judg-
ments. Committee members were obliged to interpret the concept of ethics in a
rather restricted way and they were reluctant to appear to dictate on matters of
morals to the public at large. As a result, the committee based its views on argu-
ment rather than on sentiment.
In the introduction to her book, A Question of Life (1985), Warnock wrote:
"Now, there are some respects in which a Committee of Inquiry such as ours has to
argue on utilitarian presumptions, especially with regard to legislation. By them-
selves, then, neither utilitarianism nor a blind obedience to rules could solve the
moral dilemmas the Inquiry was forced with. We were bound to have recourse to
moral sentiment, to try, that is, to sort out what our feelings were, and to justify
them."
2
The committee set the following terms of reference: "To consider recent and
potential developments in medicine and science related to human fertilization
and embryology; to consider what policies and safeguards should be applied, in-
cluding consideration of the social, ethical and legal implications of these devel-
opments; and to make recommendations."
3
By setting terms as the interests of medical-legal authorities and the patriar-
chal nuclear family, the committee provided that social and medical control of re-
productive technologies must be in the hands of expert medical specialists once
acceptable boundaries were set by legislation or licensing authority guidelines.
"Barriers, it is generally agreed, must be set up; but there will not be universal
agreement about where these barriers should be placed. The question must ulti-
mately be what kind of society can we praise and admire? In what sort of society
can we live with our conscience clear?"
4
Warnock realized that the public was extremely anxious over activities that
the committee was about to examine when she wrote: "Society, insofar as it is
a single identifiable body, has here, perhaps uniquely, a corporate reaction. It
is one of fear. People generally believe that science may be up to no good, and
must not be allowed to proceed without scrutiny, both of its objectives and of its
methods."
5
Because many expressed deep concerns about the development of the new
human-assisted reproductive technologies, the committee sought evidence from
various organizations and institutions, such as the Royal College of Obstetricians
and Gynecologists (RCOG), reflecting as many different perspectives as possible.
The committee also visited Bourn Hall, the private in vitro fertilization center of
IVF pioneers Edwards and Steptoe, in order to get a first-hand perspective on the
new technology.
The committee realized that they were to examine new reproductive technol-
ogy that included countries other than Great Britain, one that was in the process
of developing and rapidly changing worldwide. However, they limited themselves
to a Great Britain approach, rendering invisible the international scope of science
and medicine and the link to international politics. Although the committee at-
tempted to keep abreast of current developments, Warnock said that they found
7 2
THE WA RNDCK REPDRT
the task overwhelming because different countries had different cultural, moral,
and legal traditions that resulted in contrasting views. In addition, countries were
also at different stages in developmentboth of services and of a policy response.
6
Warnock' s committee divided its tasks into two parts. The first was infertil-
ity and the second was the pursuit of knowledge designed to benefit society at
large, specifically evolving scientific developments. Taking a pragmatic view that
they could react only to what they knew and what they could realistically foresee,
the committee identified four areas of major concern:
(1) Infertility as a disease, the domain of medicine
(2) The sanctity of the embryo
(3) The ideology of motherhood (surrogacy)
(4) The status of scientific (technological) knowledge
7
The Report
The Warnock Report was first published in 1984. The recommendations were in-
corporated, with certain modifications, in research and medical guidelines by the
Royal College of Obstetricians and Gynecologists, the British Medical Associa-
tion, and the Medical Research Council. Able to reach agreement on most areas,
the Committee eventually issued a list of sixty-four recommendations concern-
ing artificial techniques for assisting human reproduction.
Framing their recommendations in general terms, the committee left specific
details to be worked out by the British government and other appropriate organ-
izations. Although everything in the report seemed quite reasonable to most re-
viewers, not everything in the report was as it should be to many. Those who
reviewed the Warnock Report were divided. Most critics were angry at what they
viewed as unreasonable recommendations, whereas others viewed the Warnock
Report as a compromise.
8
Despite their differences, Warnock praised her committee members as being
extremely capable, as evidenced by their thorough investigation of scientific in-
formation and the careful wording of the Warnock Report, which proved to be a
key text, not only in Great Britain but in other countries as well. Taken as a point
of reference by medical, scientific, and legal professionals, the committee' s rec-
ommendations are even today used by many as a model for committees and
guidelines.
Acknowledging sensitivity of the issues, Warnock in a June 26, 1984, letter to
the British government wrote:
Despite the way in which members have worked together, there remain
nonetheless certain differences between us; indeed it would have been
surprising if, on such sensitive issues, we had been united. These dif-
ferences, presented in three formal expressions of dissent have, signifi-
cantly, focused on the very subjects, surrogacy and research on human
embryos, which, to judge from the evidence, arouse the greatest public
7 3
THE GENETI CS REVDLUTI DN
anxiety. Thus even in our disagreement we have reflected the range of
views within society
9
Regrettably, the committee did not feel that they were able to obtain as much
evidence as they would have liked, particularly from minority and special interest
groups. Rather than discussing in their report every situation that might arise and
then relating it to existing law, Warnock said that they considered fundamental
questions raised in relation to existing law, as well as essential legislative changes
applied equally throughout Great Britain and Nort hern Ireland.
10
The committee was silent on the use of genetic technology by the military
and was cautious on possible future developments in researchfor example,
trans-species fertilization, drug testing using embryos, cloning, parthenogenesis,
nuclear substitution, and gene replacement. The committee also avoided making
recommendations on abortion, contraception, and ectogenesis (artificial womb)
because these topics were within the terms of reference. At the time that the
committee wrote the report, they had agreed that cloning was too far in the future
to require legislation. With regard to human embryo research, they replaced
the question of When does life begin ("personhood")? with the ethical and legal
question, How is it right to treat the human embryo?
11
Infertility as a Medical Condition
The committee heard arguments for and against treatment for infertility. The
committee made known to the public that it thought of the family as a highly val-
ued institution of society and that infertility was a medical condition worthy of
study. Primary emphasis of the committee' s recommendations was on fertility as
a malfunction of couples, rather than malfunction of male or female.
Views in favor of treating infertility by assisted reproductive technologies
included a powerful urge to perpetrate an individual's genes through a new
generationa desire that could not be assuaged by adoption; social pressures
such as the feeling that couples are unable to fulfill their own and others' expec-
tations that they have children; and exclusion by contemporaries who had chil-
dren and exclusion from activities of these families.
Arguments against the treatment of infertility by assisted reproductive tech-
nologies included the view that the world was overpopulated and that it was
wrong to create by assisted reproductive technologies more human beings who
would eventually consume finite resources; that it was not only selfish to use as-
sisted reproductive technologies but that it also interfered with nature and was
against the will of God; and further, that the desire to have children by assisted
reproductive technologies was no more than a wish; it did not constitute a need.
The committee concluded that infertility was a malfunction of the human
body and one that merited treatment. They agreed that, in general, everyone
should be entitled to seek expert advice and appropriate investigation of his or
her infertility. The committee recommended that the patient always be provided
with a full explanation of the reasons he or she was denied treatment. However,
no firm opinion was offered on the provision of help with children of lesbians.
7 4
THE WARNDCK REPDRT
Overall, the treatment of infertility by assisted reproductive techniques was sup-
ported by the committee. Rejected was the need to restrict population growth.
12
Embryo Research
The committee' s major approach was embryo centered, as well as knowledge cen-
tered. All other issues were considered relatively trivial. Asked to recommend
whether embryo research should be allowed at all because of public disapproval,
the committee looked at the very earliest stages of human development, starting
with in vitro fertilization (IVF) of the egg and sperm to form the zygote and even-
tually the first recognizable features of the embryo proper.
Warnock wrote: "It was the development of IVF that, for the first time, gave
rise to the possibility that human embryos might be brought into existence which
might have no chance to implant because they were not transferred to a uterus
and hence no chance to be born as human beings. This inevitably led to an exam-
ination of the moral rights of the embryo."
13
The committee defined limits of embryo research by making two categories
of study. The first category was pure research and was designed to increase and
develop knowledge of the very early stages of the embryo. The second category
was applied research with direct diagnostic or therapeutic aims for the human
embryo or for the alleviation of infertility in general.
14
Arguments were heard for and against the use of human embryos for re-
search. The main concerns of opponents were the status of the embryo and fear of
out-of-control science or the Frankenstein image. Opponents also had major con-
cerns about scientists tampering with human life in order to create hybrids, or par-
ticipating in selective breeding and eugenic selection. Feminists complained that
the recommended restrictions on human embryo research concerned the human-
ity of embryos, not women. They felt that approval of human embryo research
boiled down to approving the use of women as laboratory animals.
15
Opponents of embryo research also felt that embryos were potentially human
and thus should have the same status as a child or an adult and should have a
chance for further development. They argued that to take the life of an innocent
embryo for research was morally unacceptable. Opponents also believed it uneth-
ical to carry out any research on human embryos without first obtaining informed
consent. Since embryos were not able to give consent, opponents felt they should
not be used for research purposes. The committee gave moral approval to IVF
only if each embryo that was produced was transferred to a uterus. Others felt
that since embryos were potentially human persons, and if "personhood" had
been established, it might be permissible for research to be undertaken.
Supporters of human embryo research argued that a human embryo could
not be thought of as an actual or even a potential person. They concluded that
the embryo was a mere collection of cells that had no potential for development
unless implanted in a uterus. Considering the embryo only as a cluster of cells,
supporters believed that the embryo did not deserve the same respect as a human
being. However, they argued that if beneficial results could be obtained from em-
bryo research then it should be done. At the time of the study, the committee
7 5
THE GENETI CS REVDLUTI DN
underestimated the speed with which it would be possible to use DNA probes for
the diagnosis of the genetic health of an embryo.
The committee had substantial difficulty in reaching an agreement on human
embryo research. Warnock wrote:
I do not believe that the question of individual freedom enters here
into public thinking. A scientist who argued that he must be free to
carry out whatever research he liked, by whatever methods, would not
get much public support, if this involved the use of other human be-
ings. Society feels, albeit obscurely, that its members, especially the
most helpless, such as children and the very old, must be protected
against possible exploitation by enthusiastic scientists; and embryos
are brought into the category of those deserving protection, just as an-
imals are. This is a matter of public, and widely shared, sentiment.
16
With regard to embryos being used for routine testing of drugs, Warnock
wrote on behalf of the committee: "We feel very strongly that the routine testing
of drugs on human embryos is not an acceptable area of research because this
would require the manufacture of large numbers of embryos. We concluded
however that there may be very particular circumstances where the testing of
such substances on a very small scale may be justifiable."
17
The committee considered biopsy as a possible future development to allow
detection of genetic abnormalities and genetic selection of embryos. It was noted
that the scientific definition of "genetic abnormality" was at the time expanding
to include "abnormalities" like cleft palate, and that the desire for "perfect" ba-
bies was being exploited by IVF researchers who argued for the superiority of ar-
tificial reproduction.
18
Embryos and the Law
Committee members agreed that human embryo research was a matter that
needed to be legislated, and the extent to which embryos were used must be a de-
cision based on law. Believing that the law must generally be seen to be beneficial,
intelligible, and enforceable, Warnock wrote: "This was the task that, especially
in the second part of the Report, the Committee had to tackle. It was a task, as I
have suggested, which raised profound and far-reaching questions about the rela-
tion between the law and the morality of society."
19
The committee concluded that the human embryo should not be accorded
the same status as a living person under current English law. They agreed, how-
ever, that human embryos should be afforded some protection in law. The com-
mittee recommended that research conducted on IVF embryos and the
handling of such embryos should be permitted only under license and that any
unauthorized use of an in vitro embryo would in itself constitute a criminal of-
fense. In making its recommendation, the committee cited the Offenses Against
the Person Act 1861, the Infant Life Preservation Act 1929, and the Abortion Act
1967.
7 6
THE WARNOCK REPDRT
Committee members could not agree over the degree of protection that the
law should afford to the human embryo. The question, according to Warnock,
was not whether the embryo was alive and human, or whether, if implanted, might
become a full human being. Committee members agreed that these things were
true. Rather, they argued that because, in practical terms, a collection of four or
sixteen cells was very different from a full human being, from a new human baby,
or from a fully formed human fetus, it might quite legitimately be treated differ-
ently. The committee did agree, however, that in some circumstances an embryo at
a very early developmental stage might be used for research purposes.
The committee recommended that no live embryo derived from in vitro fer-
tilization (frozen or unfrozen) should be kept alive, if not transferred to the
uterus of a woman, beyond fourteen days after fertilization. They also recom-
mended that it be a criminal offense to handle or use the embryo beyond that
time.
20
The limit of fourteen days after fertilization was one of many criteria sug-
gested to the Warnock Committee by consulting doctors and scientists. British
embryologist Anne McLaren, a member of the Warnock Committee, presented a
scientific explanation for the fourteen day limit. McLaren explained that for the
first two weeks after fertilization the cells of the growing "pre-embryo" are en-
gaged in making cells that eventually become the placenta and at fifteen or sixteen
days the "primitive streak" appears, where the "definitive" embryo begins to
form.
Committee members recommended regulation of IVF, artificial insemination
by donor (AID), human embryo research, and medical application of genetic
technologies through a centralized licensing authority. Any nonlicensed activity,
they concluded, would be a criminal offense. Some committee members did not
make the same distinction between spare and deliberately generated embryos and
argued that it made no difference whether the embryos just happened to be avail-
able or were created intentionally for the purpose of research. In either case,
Warnock writes, there was no potential for human life since the embryos would
not be transferred to a uterus. In either case, however, the fourteen day limitation
would be in effect.
The committee recommended that embryo research should be carried out
wherever possible with the consent of the genetic parents. Deciding to allow
cross-species experiments, the committee recommended that those embryos would
have to be destroyed after the first cell division. The transfer of human embryos
to the uteri of other species was banned outright.
The committee requested that inspectors monitor laboratory work in hu-
mans using assisted reproductive technologies. Some feminist groups countered
that the committee took the attitude of experts who state that human embryo re-
search and IVF are the antithesis of abortion, the creation of life. However,
Warnock Committee members argued that a moral couple uses technologies to
avoid abortion.
21
The committee argued that, unlike a full human being, the embryo might le-
gitimately be used as a means to an end that was good for other humans. Reason-
ing such as this became the committee's moral judgment. Warnock, in a compelling
statement on behalf of the committee, wrote:
7 7
THE GENETI CS REVOLUTI ON
What was being weighed up was certain human goods on the one hand
and the status of these collections of cells on the other. One was to be
valued against the other. The majority of the Committee was not moved
by the argument that these cells could, if certain conditions were satis-
fied, become human beings. They did not rely, that is to say, as the mi-
nority did, on "potentiality", but on the consideration of what the
embryo was at a particular time, its actual mode of existence immedi-
ately after fertilization. If, on broadly utilitarian grounds, the benefits
from the use of embryos at this stage seemed very great, and not only
was there no harm in the sense of immediately-felt pain to the embryo
but also in addition there was no absolute outrage of general moral
sentiment (as there would be, for instance, if even a very young or pro-
foundly defective child were used for research) then the majority argued
that the embryo might be used for research. The precise point of dis-
pute within the Committee was not on the value that should be attached
to human life in general, but to the value that should be attached to hu-
man life at its very earliest stage of development. It was here that it was
necessary to invoke the law.
22
The committee also discussed embryonic biopsy as a possible future research
development to detect genetic abnormalities. This was considered by some as a
eugenic approach to reproduction, and the committee directed the question of
embryonic gene therapy to the proposed licensing authority, authorizing them to
decide about such matters.
Warnock wrote:
Nevertheless, the argument runs, research on embryos may be justi-
fied, provided that the embryos used as subjects of research were
brought into being, not primarily for research, but in order to alleviate
a particular case of infertility. This argument in part rests on the doc-
trine known to philosophers as "double effect": an act which would be
wrong if chosen for its own sake may be justified if it occurs as a by-
product of some other, well-intentioned act. According to this view,
therefore, there would be no general acceptance of research on em-
bryos, but acceptance only in the limited circumstance of the exis-
tence of "spare embryos". Those who hold this view would argue that
it would be preferable on moral grounds that there should be no re-
search on embryos rather than research regardless of the circum-
stances in which the embryos were brought into being.
23
The committee decided it would be morally wrong to bring human embryos
into being with the sole intent that they be used for research. Members felt that
once a foot was set on the "slippery slope" of deliberate creation of embryos, there
would be no end to the dangers. In the case of "spare embryos," the committee rec-
ommended that no research should be carried out without the informed consent of
the couple for whom the embryo was generated. The committee recommended a
need to obtain consent to the method of use or disposal of spare embryos.
7 8
THE WA RNDCK REPDRT
Artificial Insemination by Husband or Donor
The Warnock Committee voted to consider artificial insemination (AI) because it
was neither accepted ethically nor regulated by law. Committee members decided
to propose that artificial insemination by the donor (AID) be regulated for the
same reasons and by the same licensing authority required to regulate IVF. This
meant that females who ran self-insemination groups in Great Britain would be
criminally liable. The committee concluded that AID should receive protection
of the law and should be subject to certain conditions and safeguards, that a li-
censing authority to regulate provision of AID should be established, and that
any nonlicensed activity should be a criminal offense.
24
As to eligibility for AID, the committee recommended that physicians would
be the final authority but would require a special license to offer AID. Researchers
would have access to donated sperm for genetic studies, just as they would have
access to gametes and embryos from IVF. This was interpreted by some feminist
groups as the state's desire to reassert traditionalist male authority.
25
The committee recommended that artificial insemination by husband (AIH)
or an IVF child not in utero at the date of the father's death should be disre-
garded for purposes of succession to and inheritance from the father. Anticipat-
ing unprecedented legal complications resulting from the use of frozen embryos,
they added: for the purposes of establishing primogeniture the date and time of
birth, and not the date of fertilization, shall be the determining factor.
26
At the time the Warnock Report was written neither AIH nor AID was un-
lawful. However, in 1978 Conservative Member of Parliament Rhodes Boyson
had demanded legislation to ban the use of AID by lesbians, saying: "To bring
children into the world without a natural father is evil and selfish. This evil must
stop for the sake of the potential children and society, which both have enough
problems without the extension of this horrific practice."
27
The Warnock recom-
mendations on eligibility concurred with the sentiments of Boyson.
The committee recommended that a child born to a married couple as a result
of AIH was the legitimate child of that couple. A child born as a result of AID, on
the other hand, was illegitimate, and so was liable to suffer all the disadvantages as-
sociated with that status. In theory, the husband of the woman who bore an AID
child had no parental rights and duties in law with regard to the child; rather, these
in principle lay with the donor. The committee further recommended that on
reaching the age of eighteen the child should have access to basic information about
the donor' s ethnic origin and genetic health and that legislation should be enacted
to provide the right of access to this. The legislation should not be retrospective.
28
The committee heard strong arguments against AID. Most Warnock Com-
mittee members were concerned that a third party would be introduced into
what ought to be an exclusive relationship between husband and wife. Some con-
sidered AID harmful to not only the family but to the spousal relationship because
the child would be the wife and donor' s biological child, excluding the husband
from the procreation. However, others believed that it would provide stability in
the family if the husband agreed to the procedure. After much discussion, the
committee did not accept that the donor was necessarily a threat to the stability
of the relationship.
29
7 9
THE GENETI CS REVOLUTI ON
There were equally strong arguments in favor of AID. Supporters argued
that the process allowed couples to have a child they otherwise would not have.
Since the AID child was very much desired, the committee agreed that in all like-
lihood the child would strengthen the couple' s relationship. The committee did
not encourage the possibility of prospective parents seeking donors with specific
characteristics by the use of whose semen they hoped would give birth to a par-
ticular type of child, but believed that the couple should be given sufficient in-
formation on the donor for their reassurance.
30
In Vitro Fertilization (IVF)
With regard to infertility and in vitro fertilization (IVF), Warnock wrote: "In the
days preceding in vitro fertilization the cause of infertility in a childless couple
was generally attributed to the woman; only occasionally was it thought that
there might be something wrong with the man."
31
Realizing the angst that infertility causes childless couples, Warnock, on be-
half of the committee, wrote: "For those who long for children, the realization
that they are unable to found a family can be shattering. It can disrupt their pic-
ture of the whole of their future lives."
32
The committee recognized that during the IVF pioneering days of Edwards
and Steptoe there had been a great deal of concern and anxiety over IVF. Writing
about the 1970s and the ethical debates over their pioneering IVF work, Robert
Edwards commented:
On the other hand I would not wish the reader to imagine we
[Edwards and Steptoe] were overly vulnerable. I had been a member of
a small committee for some years now that had been formed to clarify
ethical issues arising from advances in biology. Its Chairman was Wal-
ter Bodmer, Professor of Genetics at Oxford University. It included a
theologian, Gordon Dunstan, John Maddox, who was editor of
Nature, and two politicians, Shirley Williams, a future Cabinet Minis-
ter, and David Owen, a future Foreign Secretary. Doctors and scien-
tists like myself held numerous meetings and we called on many
witnesses to discuss organ transplantation, the screening of fetuses for
inherited disorders, artificial insemination and, of course, fertilization
in vitro.
33
The practice of IVF was commended by the committee, but within a frame-
work of licenses because the overall rate of success at the time of the Warnock
Report was still quite low. IVF had been originally proposed for use on women,
like Louise Brown's mother, whose infertility was caused by blocked or absent
fallopian tubes (oviducts). Today, among IVF candidates are fertile women whose
partners have low sperm counts or who do not wish, for one reason or another,
to be inconvenienced by a pregnancy.
With regard to IVF the committee' s most visible concerns were the status of
the embryo and the problem of infertility in marriage. The committee approved
SD
THE WA RNOCK REPORT
the use of IVF for infertility treatment for cohabiting heterosexual couples when
eggs that were taken from a woman were fertilized with the sperm of her partner.
The committee cited medical risks of surgical removal of eggs as an argument
against egg donation. Eventually, the committee approved egg donation because
of its social value.
Concern for the embryo was a prime argument of those who were against
IVF. One concern included more embryos brought into existence than would be
transferred to the mother' s uterusi.e., "spare embryos." Those opposed to IVF
believed it was morally unacceptable to deliberately manufacture embryos that
had the potential for human life and then to discard them if not needed or used.
The primary argument in favor of IVF was that the successful technology would
allow a childless couple to have a child.
Having substantial concerns over IVF, Warnock' s committee discussed many
significant questions. They concluded that the medical risks of IVF were not nec-
essarily more dangerous that those associated with surgical removal of eggs (both
procedures carry dangerous risks). The committee wondered why IVF should be
rejected. The evident reason, they ascertained, was the risk of unwanted preg-
nancy in the donor woman if the fertilized egg implants in her own uterine wall.
The committee was perplexed by the question, what can society do with this
other mother? The confusion of such relationships challenged the exclusivity of
marriage. They considered the fact that two women would be sharing a preg-
nancy. If the donor woman became pregnant, it would be an undesirable out-
come. It she decided to have an abortion, she would be considered not a good
woman or mother. If she carried the child to full term and kept it, the father of
her offspring would be someone else's husband. Considering these things, the
committee eventually concluded that there would be no respectable place for this
donor woman in the usual categories of motherhood.
The only argument the committee cited in favor of IVF was that it would
help infertile couples have children and was the only method by which some
could have a child that was genetically entirely theirs. This exclusive nuclear family
argument eventually convinced the committee of the importance of IVF. How-
ever, certain feminist groups countered that in the social terms of this discourse,
women did not exist; rather, motherhood was what existed.
There was a call for the creation of a new licensing authority to regulate both
research and therapy pertaining to AID and both standard and nonstandard
forms of IVF; a fourteen-day limit on the use of frozen embryos for either re-
search or therapeutic purposes; the need to obtain consent from the donor for
any interventions pertaining to embryos; and, perhaps most controversially, the
criminalization of surrogacy.
34
Egg Donation
When the Warnock Committee studied egg donation, they found that it was open
to the same kinds of objections as AIDthe introduction of a third party into the
marriage. They decided that egg donation interfered with the normal process of
fertilization, much like IVF. Proponents of egg donation argued that it provided
B l
THE GENETI CS REVDLUTI DN
an opportunity for both partners to contribute to the birth of a child, allowing the
couple the same experiences during the pregnancy as other couples have.
The committee decided that egg donation provided an offspring which was
genetically related to the husband. Egg donation also meant that women who car-
ried heritable genetic disease could avoid having to make abortion decisions by
using donor eggs. A physical risks argument was used to reject the technique of
egg donation by uterine lavage, where the donor woman conceived in vivo (in her
body), usually by artificial insemination with sperm from the husband of the re-
ceiving couple. In successful cases, the fertilized egg was "washed" from the donor' s
womb and placed in the womb of the receiving woman.
The committee considered the consequences when a woman donated an egg
for transfer to another. They concluded that egg donation should be treated as ab-
solute and that, like a male donor, the female donor should have no rights or du-
ties with regard to any resulting child. The committee recommended that when a
child was born to a woman following donation of another' s egg, the woman giv-
ing birth should, for all purposes, be regarded in law as the mother of that child,
and that the egg donor should have no rights or obligations in respect to the
child.
35
The Warnock Committee considered egg donation as ethically acceptable
where the donor was properly counseled and made aware of any risks. The com-
mittee felt that the law should treat egg donation in the same manner as AID and
IVF and that the same principles of practice should be applied to all. This in-
cluded anonymity of the donor, limitation of the number of children born from
the eggs of any one donor to ten, openness with the child about his/her genetic
origins, the availability of counseling for all parties, and informed consent.
36
Embryo Donation
The committee determined that embryo donation took two forms. The first in-
volved the donation of both an egg and semen. The egg was fertilized in vitro with
donated semen and allowed to develop to an embryo. The resulting embryo was
transferred to a woman who was unable to produce eggs and whose husband
was also infertile. The second method, called uterine lavage, did not involve re-
moving the egg by surgical intervention. In this method the egg was released nat-
urally from the ovary during the menstrual cycle. During the optimal time of
ovulation the female was artificially inseminated with semen from the husband of
the infertile woman or from a donor if the husband was also infertile.
37
Three or four days later, before the start of implantation, the donor' s uterus
was "washed out" and the embryo was retrieved. The embryo was next transferred
to the uterus of the infertile woman and allowed to implant, and the pregnancy car-
ried to term. Arguments against embryo donation included the introduction of
a third party into an exclusive relationship. The committee also considered the fact
that when a semen donor was used neither of the nurturing parents had con-
tributed genetically to the child.
The committee felt that embryo donation was probably the least satisfactory
form of donation. Believing that there would be a minimal number of embryo
B 2
THE WA RNOCK REPORT
donations, the committee recommended that it be accepted as a treatment for in-
fertility, subject to the same type of licensing and controls as AID, IVF, and egg
donation. The committee also recommended that it should be accepted practice
to offer donated gametes and embryos to those at risk of transmitting hereditary
disorders. Primarily because of the risk to the egg donor, the committee did not
recommend embryo donation by lavage.
Surrogacy
In writing their official recommendations, the question of surrogacy presented
the committee with some of the most difficult problems they were to encounter.
After considerable discussion, the committee unanimously agreed that surrogacy
for convenience alonefor example, where a woman did not want to undergo
pregnancy because she was deeply involved with her careerwas totally unac-
ceptable. The committee concluded that the exploitation of another individual
outweighed the potential benefits.
The committee agreed that criminal law should be involved in the control of
surrogacy and recommended that legislation be introduced to render criminal
the creation or the operation of surrogacy. Recommendations included making
criminally liable the actions of professionals and others who knowingly assisted
in the establishment of surrogate pregnancy, and that it be provided by statute
that all surrogacy agreements be illegal contracts and therefore unenforceable in
the courts.
Rejecting surrogacy, the committee reported that "the weight of public opin-
ion is against the practice and recommends the criminalization of organized sur-
rogacy arrangements, referring to the activity as ' recruitment of women.' "
38
Arguments against surrogacy all addressed the same issuethe meaning of
motherhood and woman' s sexuality:
To introduce a third party into the process of procreation which
should be confined to the loving partnership between two people, is
an attack on the value of the marital relationship;
it (surrogacy) is inconsistent with human dignity;
the relationship between mother and child is itself distorted by surro-
gacy;
this is the wrong way to approach pregnancy;
since there are some risks attached to pregnancy, no woman ought to
be asked to undertake pregnancy for another, in order to earn money.
Nor, it is argued, should a woman be forced by legal sanctions to
part with a child, to which she has recently given birth, against her
will.
39
The committee drew a firm line on the practice of surrogate motherhood
where the mothers did not intend to keep the child. They based their decisions
chiefly on emotional and legal difficulties but also on fears of "commercial
8 3
THE GENETI CS REVDLUTI DN
exploitation."
40
However, members of the committee did feel there was some
place for surrogacy in special circumstances. In 1986, IVF pioneers Patrick Step-
toe and Robert Edwards also suggested that surrogacy be allowed in special
circumstancesfor example, when a sister or relative of an infertile couple in
their IVF program was willing to become a surrogate mother. For example, Step-
toe and Edwards asked: "Why should a childless woman with a hysterectomy be
denied the chance of a child with the willing help of another woman, perhaps a
sister?"
41
In deciding on surrogacy, the committee agreed unanimously on the disap-
proval of surrogate motherhood, largely because of possible consequences for
the child. They agreed, however, that surrogacy could not be prevented by law be-
cause of the intrusiveness of any law that would be impossible to enforce. By a
majority vote, the committee recommended that the commercial use of surro-
gacy arrangements, as a way of making money for an agency, could and should be
made a criminal offense. The 1985 Surrogacy Arrangements Act criminalized surro-
gacy in Great Britain.
Two members of the committee, Wendy Greengross and David Davies, dis-
sented from the majority opinion to ban surrogacy. However, they did express
concerns over surrogacy, saying they believed it could lead to serious problems.
They agreed with the rest of the committee that criminal law should prevent
profit making using surrogates and that surrogacy for convenience should not be
allowed. Many doctors and IVF practitioners opposed the committee' s rejection
of surrogacy, and in 1985 a small majority of members of the British Medical As-
sociation (BMA) voted in favor of surrogacy as a medical treatment for infertility,
against BMA official policy.
The committee reported that "supporting research on the prevention of ge-
netic defect is one thing; supporting research for high tech, state controlled, arti-
ficial reproduction, at the expense of women' s bodies, for the sake of producing
superior offspring, is another."
42
Freezing and Storage of Human Semen,
Eggs, and Embryos
The committee did not object to the freezing of human semen, eggs, and embryos
in the treatment of infertility and recommended the use of frozen semen in artifi-
cial insemination. However, subject to review by the licensing body, they recom-
mended that the use of frozen eggs in therapeutic procedures not be undertaken
until research showed that there was no risk. The committee also recommended
that the clinical use of frozen embryos should continue to be developed under re-
view by the licensing body.
The committee recommended that five-yearly reviews of deposited eggs and
semen be made. They also recommended that legislation provide that when a per-
son dies during the storage period or cannot be traced at a review date the right of
use or disposal of his or her frozen gametes should pass to the storage authority.
It also discouraged the use by a widow of her dead husband' s semen for artificial
insemination.
B 4
THE WA RNDCK REPDRT
Wi t h regard t o storage of embr yos for future use, t he commi t t ee r ecommended
a ma xi mum of t en years, after whi ch t i me t he ri ght t o use or di sposal shoul d pass
t o t he st orage aut hor i t i es. However, t he coup l e who st ored t he embr yo shoul d
have l i mi t ed ri ght s t o t he use and di sposal of t he embr yo. If t her e was a mar i t al
br eakdown, it was r ecommended t hat t he use or di sposal of t he embr yo shoul d
pass t o t he st orage aut hor i t y as t hough t he t en-year p er i od had expi red.
The commi t t ee r ecommended no ri ght t o owner shi p of a h u ma n embr yo, as
di rect ed by legislation. Wi t h regard t o t he quest i on of i nher i t ance and succes-
si on, t he commi t t ee r ecommended t hat for t he p ur p os es of est abl i shi ng p r i mo-
geni t ure t he dat e and t i me of bi r t h, and not t he dat e of fertilization, shoul d be
t he det er mi ni ng factor.
Official Recommendations
The commi t t ee acknowl edged t hat many of its r ecommendat i ons were undul y
lax but were justified by t hei r relevance t o beneficial medi cal t r eat ment s for infer-
tility.
43
Listed bel ow are t he commi t t ee' s official r ecommendat i ons :
A. The licensing body and its functions
1. A new statutory licensing authority be established to regulate both re-
search and those infertility services which we have recommended should
be subject to control.
2. There should be substantial lay representation on the statutory authority
to regulate research and infertility services and that the chairman must be a
lay person.
3. All practitioners offering the services we have recommended should only
be provided under license, and all premises used as part of any such provi-
sion, including the provision of fresh semen and banks for the storage of
frozen human eggs, semen and embryos should be licensed by the licensing
body.
4. AID should be available on a properly organized basis and subject to the li-
censing arrangements, to those infertile couples for whom it might be ap-
propriate. The provision of AID services without a license for the purpose
should be an offense.
5. The service of IVF should continue to be available, subject to the same type
of licensing and inspection as we have recommended with regard to the reg-
ulation of AID.
6. Egg donation should be accepted as a recognized technique in the treat-
ment of infertility subject to the same type of licensing and controls as we
have recommended for the regulation of AID and IVF.
7. The form of embryo donation involving donated semen and egg which are
brought together in vitro be accepted as a treatment for infertility, subject
to the same type of licensing and controls as we have recommended with
regard to the regulation of AID, IVF, and egg donation.
8. The technique of embryo donation by lavage should not be used at the
present time.
8 5
THE GENETI CS REVDLUTI DN
9. The use of frozen eggs in therapeutic procedures should not be under-
taken until research has shown that no unacceptable risk is involved. This
will be matter for review by a licensing body.
10. The clinical use of frozen embryos may continue to be developed under
review by the licensing body.
11. Research conducted on human in vitro embryos and the handling of such
embryos should be permitted only under license.
12. No live human embryo derived from in vitro fertilization, whether frozen
or unfrozen, may be kept alive, if not transferred to a woman beyond
fourteen days after fertilization, nor may it be used as a research subject
beyond fourteen days after fertilization. This fourteen day period does
not include any time during which the embryo may have been frozen.
13. Consent be obtained as to the method of use or disposal of spare
embryos.
14. As a matter of good practice no research should be carried out on a spare
embryo without the informed consent of the couple for whom the embryo
was generated, whenever this is possible.
15. Where trans-species fertilization is used as part of a recognized program
for alleviating infertility or in the assessment or diagnosis of sub-fertility
it should be subject to license and that a condition of granting such a li-
cense should be that the development of any resultant hybrid should be
terminated at the two-cell stage.
16. The licensing body be asked to consider the need for follow-up studies of
children born as a result of the new techniques, including consideration
of the need for a centrally maintained register of such births.
17. The sale or purchase of human gametes or embryos should be permitted
only under license from, and subject to, conditions prescribed by the li-
censing body.
B. Principles of provision
18. As a matter of good practice any third party donating gametes for infer-
tility treatment should be unknown to the couple before, during and after
the treatment, and equally the third party should not know the identify
of the couple being helped.
19. Counseling should be available to all infertile couples and third parties at
any stage of the treatment, bot h as an integral part of NHS provision and
in the private sector.
20. On reaching the age of eighteen the child should have access to the basic
information about the donor' s ethnic origin and genetic health and that
legislation be enacted to provide the right of access to this.
21. In the case of more specialized forms of infertility treatment the consent
in writing of bot h partners should be obtained, wherever possible, before
treatment is begun, as a matter of good practice. Any written consent
should be obtained on an appropriate consent form.
22. The formal consent in writing by both partners should, as a matter of
good practice, always be obtained before AID treatment begins. A con-
sent form should be used and thoroughly explained to both partners.
B 6
THE WARNDCK REPORT
23. For the present, there should be a limit of ten children who can be fa-
thered by one donor.
24. In cases where consultants decline to provide treatment they should al-
ways give the patient a full explanation of the reasons.
25. The NHS numbers of all donors be checked by the clinics where they
make their donations against a new centrally maintained list of NHS num-
bers of existing donors, which is to be held separately from the NHS
donor register.
26. There should be a gradual move towards a system where semen donors
should be given only their expenses.
27. In relation to egg donation the principles of good practice we have already
considered in relation to other techniques should apply, including the
anonymity of the donor, limitation of the number of children born from
the eggs of any one donor to ten, openness with the child about his genetic
origins, the availability of counseling for all parties and informed consent.
28. It should be accepted practice to offer donated gametes and embryos to
those at risk of transmitting hereditary disorders.
29. All types of "do-it-yourself" sex selection kits should be brought within
the ambit of control provided by the Medicines Act with the aim of en-
suring that such products are safe, efficacious and of an acceptable stan-
dard for use.
30. The use of frozen semen in artificial insemination should continue.
31. There should be automatic five-yearly reviews of semen and egg deposits.
32. There should be a maximum of ten years for the storage of embryos after
which time the right to use or disposal should pass to the storage authority.
33. When one of a couple dies the right to use or dispose of any embryo
stored by that couple should pass to the survivor. If both die that right
should pass to the storage authority.
34. Where there is no agreement between the couple the right to determine
the use or disposal of an embryo should pass to the storage authority as
though the ten year period had expired.
C. Service provision
35. Funding should be made available for the collection of adequate statistics
on infertility and infertility services.
36. Each health authority should review its facilities for the investigation and
treatment of infertility and consider the establishment, separate from
routine gynecology, of a specialist infertility clinic with close working re-
lationships with specialist units, including genetic counseling services, at
regional and supra-regional level.
37. Where it is not possible to have a separate clinic, infertility patients should
be seen separately from other types of gynecological patients, wherever
possible.
38. The establishment of a working group at national level made up of cen-
tral health departments, health authorities and those working in infertil-
ity, to draw up detailed guidance on the organization of services.
B7
THE GENETI CS REVDLUTI DN
39. Consideration be given to the inclusion of plans for infertility services as
part of the next round of health authority strategic plans.
40. IVF should continue to be available within the NHS.
41. One of the first tasks of the working group, whose establishment we rec-
ommend, should be to consider how best an IVF service can be organized
within the NHS.
D. Legal limits on research
42. The embryo of the human species should be afforded some protection
in law.
43. Any unauthorized use of an in vitro embryo would in itself constitute a
criminal offense.
44. Legislation should provide that research may be carried out on any em-
bryo resulting from in vitro fertilization, whatever its provenance, up to
the end of the fourteenth day after fertilization, but subject to all other
restrictions as may be imposed by the licensing body.
45. It shall be a criminal offense to handle or to use as a research subject any
live human embryo derived from in vitro fertilization beyond that limit
(i.e., fourteen days after fertilization).
46. No embryo which has been used for research should be transferred to a
woman.
47. Any unlicensed use of trans-species fertilization involving human ga-
metes should be a criminal offense.
48. The placing of a human embryo in the uterus of another species for ges-
tation should be a criminal offense.
49. The proposed licensing body promulgates guidance on what types of re-
search, apart from those precluded by law, would be unlikely to be con-
sidered ethically acceptable in any circumstances and therefore would not
be licensed.
50. Unauthorized sale or purchase of human gametes or embryos should be
made a criminal offense.
E. Legal changes
51. The AID child should in law be treated as the legitimate child of its
mother and her husband, where they have both consented to the treat-
ment.
52. A change in the law so that the semen donor will have no parental rights
or duties in relation to the child.
53. Following the English Law Commission, that it should be presumed that
the husband has consented to AID, unless the contrary is proved.
54. The law should be changed so as to permit the husband to be registered
as the father (see #51).
55. Legislation should provide that when a child is born to a woman follow-
ing donation of another' s egg the woman giving birth should, for all pur-
poses, be regarded in law as the mother of that child, and that the egg
donor should have no rights or obligations in respect to the child.
THE WA RNOCK REPDRT
56. The legislation proposed should cover children born following embryo
donation (see #53 and #54).
57. Legislation should be introduced to render criminal the creation or the
operation in the United Kingdom of agencies whose purposes include the
recruitment of women for surrogate pregnancy or making arrangements
for individuals or couples who wish to utilize the services of a carrying
mother; such legislation should be wide enough to include both profit and
non-profit making organizations.
58. Legislation should be sufficiently wide enough to render criminally liable
the actions of professionals and others who knowingly assist in the estab-
lishment of a surrogate pregnancy.
59. It should be provided by statute that all surrogacy agreements are illegal
contracts and therefore unenforceable in courts.
60. Legislation should provide that where a person dies during the storage
period or cannot be traced at a review date the right of use or disposal of
his or her frozen gametes should pass to the storage authority.
61. Legislation be introduced to provide that any child born by AIH who was
not in utero at the date of the death of its father shall be disregarded for
the purposes of succession to and inheritance from the latter.
62. Legislation be enacted to ensure there is no right of ownership in a hu-
man embryo.
63. For the purposes of establishing primogeniture the date and time of birth
and not the date of fertilization shall be the determining factor.
64. Legislation be introduced to provide that any child born following IVF,
using an embryo that had been frozen and stored, who was not in utero at
the date of the death of the father shall be disregarded for the purposes
of succession to and inheritance from the latter.
44
Reactions to the Warnock Report
The anci ent Italian syst em says t hat it is a good t hi ng t hat we have i nt ui t i ons. In
t he case of t he Wa r noc k Rep or t , however, i nt ui t i ve feelings ranged from out rage
and shock t o i nt ol er ance and di sgust . Publ i c concer ns cent ered ar ound t wo ma-
j or facet st he loss of embr yos after t ransfer t o t he ut er us (an essent i al st ep in
t he I VF process) and t he loss of embr yos t hat were not t ransferred.
Wa r noc k and her commi t t ee were aware t hat negative feelings challenged
t hei r r ep or t . In a June 26, 1984, l et t er t o t he Bri t i sh gover nment , Wa r noc k said:
It is not possi bl e t hat a r ep or t like t hi s shoul d be equal l y well received
in all quar t er s, given s ome of t he cont r over si al issues we have had t o
consi der. Ther e is bound t o be cri t i ci sm t hat we have gone t oo far, or
not far enough. However, we have sought t o p r ovi de on t he one hand
a r easoned di scussi on of t he issues whi ch we hop e will cont r i but e t o a
hi gh st andar d of publ i c debat e on mat t er s whi ch are of deep concer n
t o t he publ i c, and on t he ot her a coher ent set of p r op osal s for how
publ i c policy, r at her t han t he i ndi vi dual consci ence, shoul d r es p ond t o
B9
THE GENETI CS REVDLUTI DN
a range of developments which many people will not wish to participate
in, but which others find entirely acceptable. We have tried in short, to
give due consideration both to public and to private morality.
45
The heated and critical reactions that greeted the Warnock Report gave pause
to those in the United States who believed that the time had come to initiate reg-
ulation or legislation with respect to in vitro fertilization.
46
Most Members of Parliament in Great Britain felt that the recommendations
were too permissive, whereas many prominent scientists and scientific societies
thought it too restrictiveparticularly the recommendations concerning human
embryo research. Legal authorities in particular did not like the committee' s
stance on surrogacy and the commercialization of in vitro fertilization.
47,48
Feminists were unhappy with parts of the Warnock Report, stating that al-
though the public and others were invited to submit evidence no women' s group
had been asked to present oral evidence. This included the main artificial insemi-
nation (AI) agency in Great Britain (British Pregnancy Advisory Service) and the
largest infertility clinic in Great Britain (Hammersmith Hospital).
49
Feminist groups challenged the committee' s ruling that AID and IVF should
be made available in Great Britain to treat infertility, but only for the heterosex-
ual couple living together in a stable relationship.
50
In response to this concern,
the Warnock Committee issued a statement saying that they believed as a general
rule it was better for children to be born into a two-parent family, with both fa-
ther and mother.
51
In general, the scientific community enthusiastically accepted regulation of
AID. Although they argued for less regulation of human embryo research in the
name of scientific freedom, they endorsed the recommendations to regulate AID.
In one report, the editors of Nature said that the committee proposals on AID
were "less stringent than they might be" because genetic data about donors
should be available to researchers.
52
The scientific establishment's response to the
Warnock Report was: less regulation for embryo research in the interests of sci-
ence but more regulation for AID, again in the interests of science.
9 D
PART III
Fighting to Save a
Gene Pool
Ethnic history lies hidden within our DNA. The Human Genome Diversity Pro-
ject (HGDP) began as an international study intended to collect and preserve ge-
netic material from a portion of the world' s indigenous peoples. Among the
many values proposed for the HGDP were an understanding of human history
and identity, human biological history, and biological relationships among vari-
ous human groups. However, the HGDP has been enmeshed in massive contro-
versy since its beginnings, with intense negative reactions from many of the
indigenous peoples it had intended to study.
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6
THE HUMAN GENDME
DIVERSITY PRDJECT
The goal of the Human Genome Diversity Project is to increase
the body of scientific knowledge about all the earth' s peoples.
Existing research efforts on human genetics have focused almost
exclusively on citizens of the United States and Western Europe,
yet we know that all populationsand, indeed, all humans,
are, to some extent, genetically distinctive. Much of that distinc-
tiveness is disappearing, sometimes through physical extinction,
more often through migration, assimilation, and intermarriage.
Luigi Luca Cavalli-Sforza, Department of Genetics,
Stanford University and Henry Greely, Stanford
University Law School and Chair, HGDP North
American Regional Committee's Ethics Subcommittee
There is a marvelous diversity amongst human beings. A quick glance around any
public gathering will attest to the physical diversity of the human population.
This is what makes life and the human species so wonderful. In large measure,
physical appearance is determined by our genes (packets of DNA), which make up
forty-six chromosomes in each human cell. Collectively, these genes are known as
the human genome.
Ethnic History
Ethnic history, with its differences and similarities between various peoples and
populations, lies hidden within our DNA. Regardless of where or how people
THE GENETI CS REVDLUTI DN
live, each of their cells contains genes that transmit heritable traits from parents
to children. As a result, in most groups of people, some will be tall, others short;
some will have brown eyes, others green or blue. The study of this variation is the
basis of the study of evolution, one of the principal aims of genetics.
1
A wide enough sampling of DNA has made it possible to reconstruct human
evolution, trace global migrations, and answer questions that have concerned an-
thropologists and historians for centuries. People who live in a certain area of the
world, or who make up an ethnic group, a nation, or a population and share com-
mon ancestors are more likely to share certain kinds of genetic variants than peo-
ple who do not share common ancestors. At times, particular genetic variants can
lead to susceptibility or resistance to disease and may explain why some groups of
people resist disease better than others. Because of this, genes are of great interest
to medical researchers trying to improve human health and welfare.
2
People within certain ethnic groups are genetically more different from each
other than their group is from other groups. Researchers have shown that, in pop-
ulations studied, Europeans were an admixture of primitive African and primi-
tive Oriental populations.
3
Yet, as far as is currently known, no particular genes
make a person Norwegian or Japanese or Cherokee. These are not genetic labels,
but rather cultural ones. Although these people are more likely to have some vari-
ant genes in common, none will be found in members of one population and not
in members of any other population. In effect, there is no such thing as a gene-
tically "pure" human population.
It is not surprising to find rare variations in populations. Hundreds of distinct
ethnic groups and tribes are disappearing through intermarriage, famine, and dis-
ease. Whereas much of the world worries about pollution and saving the rain
forests, another valuable source of biological diversity is quietly disappearing
the human being. It is estimated there are about 4,000-8,000 indigenous groups
of distinct populations in the world, totaling over 600 million people, and that in
the next three or four decades at least 500 groups will be gone. Along with their
disappearance their genes will disappear, loaded with information about evolu-
tion and human physiology.
4
The Human Genome Diversity Project
In 1991 a group of prominent Bay Area human geneticists and molecular biolo-
gists, led by population geneticist Dr. Luigi Luca Cavalli-Sforza of Stanford
University, proposed to the scientific community that a five-year international proj-
ect be undertaken to study variation in the human genome. The study was intended
to be an effort to collect and preserve DNA from at least 500 of the world's endan-
gered populations, such as the Yanomami of the Amazon rain forests and the Kurds
of eastern Turkey.
For many years, Cavalli-Sforza and other geneticists and anthropologists had
collected blood and tissue samples from various ethnic groups around the world.
Their mission at that time was to create a central repository and free representa-
tive database for scientists as to how different human populations are related to
each other.
5
Cavalli-Sforza had worked for many years with populations in central
9 4
THE HUM A N GENDM E DI VERSI TY PRDJECT
Africa and had quickly discovered that many of the people he saw suffered from
yaws, a rare but terrible skin disease. On subsequent trips, in a heartening hu-
manitarian effort, he and his team brought large amounts of antibiotics to cure
people of this affliction.
In the 1980s Cavalli-Sforza and population geneticist Kenneth Kidd of Yale
University collected samples from fifteen human populations, including African
Pygmies, the Thoti of central India, Cambodians, Melanesians, and Ethiopian
Jews. Cavalli-Sforza and Kidd removed white blood cells from each person in the
study, cultured the cells in the laboratory, and then froze the cells in liquid nitro-
gen. Since each white blood cell contained DNA, the genes were preserved indef-
initely for further study.
For a very long time, scientists had been aware that each ethnic community
may have a slightly different genetic composition. Because of this, they were in-
terested in finding out if such variation in anatomy and physiology, as well as a
variation in susceptibility to disease that they knew varied from one population
to another, was caused by human adaptation to local environments or changes in
genetic makeup.
In 1991, Cavalli-Sforza and a number of colleagues wrote a letter to the edi-
tors of the scientific journal Qenomics, pointing out the need for a systematic
study of the whole range of human genetic diversity:
The populations that can tell us most about our evolutionary past are
those that have been isolated for some time, are likely to be linguisti-
cally and culturally distinct and are often surrounded by geographic
barriers. Such isolated populations are being rapidly merged with their
neighbors, however, destroying irrevocably the information needed to
reconstruct our evolutionary history.
6
The letter was signed by Cavalli-Sforza; molecular anthropologist Allan Wil-
son and geneticist Mary-Claire King, both of the University of California-
Berkeley; Charles Cantor of Lawrence Berkeley Laboratory; and Robert Cook-
Deegan of the Institute of Medicine in Washington, D.C. This led to an
informational discussion among a group of individuals attending the Interna-
tional Congress of Human Genetics meeting in Washington in late 1991, which
included representatives from the National Science Foundation, National Insti-
tutes of Health, and the Department of Energy.
Walter Bodmer, a popular geneticist and at the time president of the Human
Genome Organization (HUGO), a nonprofit, nongovernmental consortium of
scientists involved in the Human Genome Project (HGP), responded to Cavalli-
Sforza's proposal for a diversity study. Bodmer suggested the establishment of an
ad hoc subcommittee of HUGO, under the Chairmanship of Cavalli-Sforza, to
consider how such a global project could be developed. In turn, the council nom-
inated Bodmer to liaise with the committee on their behalf. Members of the ad
hoc committee included: Dr. Julia Bodmer (UK), Dr. Walter Bodmer (UK),
Dr. Luigi Luca Cavalli-Sforza (U.S.), Dr. Mary-Claire King (U.S.), Dr. Marc Feld-
man (U.S.), Dr. Ken Kidd (U.S.), Dr. Ken Weiss (U.S.), Dr. Alberto Piazza (Italy),
Dr. Marcello Siniscalco (Italy), and Dr. Svante Paabo (Germany).
9 5
THE GENETI CS REVDLUTI DN
The primary plan of the five-year diversity project was to select genetically
distinct indigenous populations worldwide and then to collect DNA and search
for DNA sequences that could potentially offer clues to genetically caused dis-
eases and cures. In addition, project scientists planned to map human genetic
diversity to give insights into the origins of modern humans as well as the move-
ments of ancient populations.
At a time when scientists were increasingly concerned with preserving infor-
mation about the diversity of many species, Cavalli-Sforza emphasized that sci-
ence should not ignore the diversity of our own species. In his letter to Qenomics
Cavalli-Sforza noted that since many ethnic groups previously had been ex-
ploited by outsiders, it was possible that these same indigenous groups might
view the diversity study as another form of exploitation. Because of this, HGDP
organizers thought it essential that the diversity project promise to provide direct
medical services as part of the sampling when it could do so.
7
Cavalli-Sforza and colleagues asked for support from national funding agen-
cies. In the United States these included the National Science Foundation, the
National Institute of General Medical Sciences, the National Center for Human
Genome Research, and the genome program at the Department of Energy. Inter-
national organizations included UNESCO, World Health Organization, and
United Nations Industrial Development Organization.
It soon became quite evident that the project would be of interest to scien-
tists and nonscientists alikehuman geneticists, linguists, historians, bimolecular
scientists, archaeologists, evolutionists, and anthropologists. Organized in mid-
September 1993, the project became known as the Human Genome Diversity Pro-
ject (HGDP) and involved national and international scientific and nonscientific
groups. The HGDP was really an initiative rather than a project, however, since it
had no initial funding.
In January 1994 the HGDP was formally brought under the auspices of the
Council of HUGO. An international executive committee coordinated the HGDP,
as well as a number of self-organized regional committees. Henry Greely, a lawyer
at Stanford University, was selected to chair the ethics subcommittee of the
Nort h American Committee.
The HGDP Executive Committee encouraged each region of the world to
create its own regional HGDP committee responsible for raising funds and over-
seeing collection efforts in their own region. Some of the regional committees
were successful in raising funds; others were not. For example, when it was first
organized, the Nort h American Regional Committee had no funding, but eventu-
ally was successful in collecting some money. On the other hand, the European
Committee received substantial operational funding from the European Commu-
nity, in addition to raising some on its own.
International Workshops
A small series of international workshops was held in order to explore major sci-
entific issues involved. The first two planning workshops were held in the United
States in 1992. Help and support for the workshops were given by the National
9 6
THE HUM A N GENDM E DI VERSI TY PRDJECT
Science Foundation, the National Center for Human Genome Research, the Na-
tional Institutes of Health (National Institute of Medical Sciences), the Center
for Human Genome Research, and the Department of Energy.
The first workshop, organized by Cavalli-Sforza and Marc Feldman, was held
at Stanford University and was concerned with the statistical issues of sampling
populations. The second workshop, organized by Ken Weiss, was held at Pennsyl-
vania State University in November 1992 and focused exclusively on anthropo-
logical issues. The primary purpose of the Penn State workshop was to identify
those issues most pertinent to representative populations from each area of the
world that met the defined criteria.
An additional meeting was held at the end of 1992 at the National Institutes
of Health in Washington, D O , to discuss technical and ethical issues connected
with the HGDP. Other discussions of the HGDP took place in various countries
during 1992, under the auspices of the Council of HUGO. These included the
Human Genome 92 meeting in Nice (France), the second HUGO Europe meeting
in Porto Conte, Sardinia (Italy), and the first South/North Human Genome meet-
ing in Brazil.
The third and main workshop was held in Sardinia on September 11-12,
1993. With wide international participation, the meeting was devoted entirely to
the global HGDP. Eighty people attended, representing twenty countries (includ-
ing the United States). The meeting was organized by HUGO Europe and repre-
sentative populations were also included in this workshop. Two parallel workshops
were held on September 9-10, 1993. One of the parallel workshops was con-
cerned specifically with the development of the global HGDP, whereas the other
one was concerned with issues of importance to anthropologists and involved ex-
tensions of discussions that had begun at Pennsylvania State University.
It was decided by participants at the workshops that pilot projects should be
completed before beginning a full-scale HGDP. Pilot projects included improving
DNA techniques and clarifying cross-cultural ethical and legal issues. It was also
decided that pilot projects should investigate what was important to populations,
particularly collection of tissue samples and cultural information. Relevant con-
cerns involved identifying culturally appropriate contacts, negotiating contracts,
maintaining continued interactions, and identifying participant concerns regard-
ing use of data and samples. It was also decided that improvements would be
needed to create affordable, distributable DNA banks.
Proposed Value of the HGDP
Broad humanitarian benefits were the primary value of the HGDP since all hu-
man groups seemed interested in their origins and scientific evidence about those
origins. In general, the HGDP was designed to help see how closely humanity is
intertwined by collecting, studying, and preserving the diversity of the genetic in-
heritance of the human species.
Other proposed specific values of the HGDP included the understanding of
human history and identity, human biological history, and biological relationships
among different human groups. These included the evolution and migration of
9 7
THE GENETI CS REVDLUTI DN
different human populationscreating a definitive "family tree" of human pop-
ulations. It was decided that some populations might be interested in what DNA
samples had to present with regard to historical stories and would allow the pop-
ulations to trace their connections to other populations and to their ancestors'
migrations.
In a July 8, 1993, statement supporting the HGDP, Greely and Cavalli-Sforzi
issued the following statement:
The goal of this project is to increase the body of scientific knowledge
about all the earth' s peoples. Existing research efforts on human gene-
tics have focused almost exclusively on citizens of the United States
and Western Europe, yet we know that all human populationsand,
indeed, all humansare, to some extent, genetically distinctive. Much
of that distinctiveness is disappearing, sometimes through physical ex-
tinction, more often through migration, assimilation, and intermar-
riage.
8
Although the primary purpose of the HGDP was cultural, it was proposed
that HGDP data would be used to study diseases and to lend aid in the treatment
and possibly the cures of these diseases, as well. Included were specific popula-
tions that were known to suffer from genetic diseases such as thalassemia in
Mediterranean populations, diabetes mellitus in Native Americans, and sickle-
cell anemia in African Americans.
On September 16, 1996, Mary-Claire King, representing the Nort h American
Regional Committee of the Human Genome Diversity Project, issued a state-
ment to the National Academy of Sciences committee on the relevance of the
HGDP:
Good afternoon. Thank you for permitting me to speak in this
public meeting. My colleague John Moore and I represent the Nort h
American Regional Committee of the Human Genome Diversity Pro-
ject. I am American Cancer Society Professor of Genetics and Medicine
at the University of Washington. My research and teaching interests lie
in human genetics, in particular how molecular genetics and genomics
can be integrated with approaches from population genetics and epi-
demiology to address problems of complex human diseases and ques-
tions of human evolution and diversity. I have been interested in these
questions for 25 years, since I was a graduate student in Allan Wilson' s
laboratory at UC, Berkeley, where our work focused on human evolu-
tion at the molecular level.
Since then, my lab has studied problems of complex human dis-
ease traits, especially breast and ovarian cancer, inherited deafness,
systemic lupus erythematosus, and AIDS. We have tried to contribute
to and use information about the human genome to identify genes
critical to the development of diseases such as breast cancer, then to
take the normal alleles of the same genes as the basis for developing
cures. I'll return to this theme of complex diseases in a moment.
9 8
THE HUM A N GENOME DI VERSI TY PRDJECT
In parallel with our work on specific diseases, we have had the op-
portunity to apply molecular genetics to problems of human rights.
We have worked since 1983 with the Abuelas de la Plaza de Mayo to
identify their grandchildren kidnapped by military squads in Ar-
gentina during the Dirty War, to learn who these children are, to re-
t urn them to their families, andin some casesto bring their
kidnappers to justice. As soon as PCR was developed, we applied
mitochondrial DNA sequencing, in the context of human diversity,
specifically to the project with the Abuelas. This was an outgrowth, of
course, of the evolutionary studies based on mitochondrial DNA se-
quencing of PCR products in the Wilson lab.This human rights work
in Argentina was one of the first projects supported by the then-very-
new ELSI Committee of the Human Genome Project. It has also been
supported by Amnesty International. The project continues to the
present, with identification of now-adult children who represent them-
selves as possible members of the disappeared.
We have applied the approaches we developed with the Abuelas to
other problems of human rights, including identification of victims of
military murders in Chiapas, in Salvador, and in Somalia, and to the
identification of MIAs from World War II, Korea, and Vietnam. We
are now working on behalf of the United Nations War Crimes Tri-
bunal to identify murder victims from Bosnia and Rwanda. This work
is supported by the United Nations through Physicians for Human
Rights.
What does all this have to do with the Human Genome Diversity
Project? The connection is that we can use the tools of molecular ge-
nomics and population genetics to answer questions about ourselves.
An important class of these questions are those of complex diseases
of people. In recent years, there has been a great deal of progress in the
identification of genes that influence diseases like cystic fibrosis, some
rare familial cancers, some common cancers, some inherited blindness
and deafness, and many others. We are beginning to learn how to use
these genes for prevention and cure.
The biggest challenges are the complex diseases: that is, diseases
for which more than one gene, as well as environmental exposures, are
likely to influence the appearance of symptoms in each ill person. Dis-
eases like this include diabetes, rheumatoid arthritis, and hyperten-
sion, to name just three. How are we to disentangle the multiple causes
of these diseases? An approach that is proving successful is to work
with relatively isolated groups of people in whom the disease is com-
mon, with the hope that the picture may be clearer in a group in whom
relatively few, relatively ancient mutations may be responsible for a
portion of the genetic influence on the disease.
Of many current examples of this approach, one published last
week is a study of diabetes in a linguistically isolated community in
the Botnian region of western Finland. In a subset of families with di-
abetes in this geographic area, in a segment of chromosome 12 about
9 9
THE GENETI CS REVDLUTI DN
20 million base pairs in length appears to be shared by relatives with
this disease. Now the problem is to close in on this gene and isolate it.
However, for this and other complex diseases, isolating genes will be
difficult, because no informative recombination events remain to de-
crease the size of the linked region.
To identify these complex disease genes, then, one must rely on the
association of genetic markers with diseases, or genetic disequilibrium.
Genetic disequilibrium is the association of specific DNA sequences,
or markers, with one another in populations. Genetic disequilibrium
depends on (1) the physical distance between the marker and the dis-
ease allele; (2) polymorphism of the marker, or how variable the marker
is; (3) mutation rate at the marker, or how fast the variation changes;
and (4) recombination rate as a function of physical distance for this
specific part of the genome. Some of these parameters depend, in turn,
on features of populations; specifically (1) effective population size; (2)
degree of endogamy; and (3) age of the disease allele in the population.
Another way of phrasing this question is: given linkage and dise-
quilibrium between markers and a hypothetical disease allele over a
large genomic region, where is the best place in that genomic region to
start looking for the disease gene? Twenty million base pairs is very
large to scan for individual mutations, even when the genome sequence
for one amalgamated person is known.
In order to narrow the search, it will be important to know more
about genomic structure at the population level. The way to learn ge-
nomic structure at the population level is to study various genomic re-
gions in different populations, with each genomic region evaluated at
markers very densely distributed. The goal of this approach is to evalu-
ate disequilibrium among markers (at different distances apart and with
different mutation rates) across the genome in populations differing in
size, endogamy, and history. In other words, how is disequilibrium dis-
tributed in the genome, as a function of (1) features of individual variant
sites, (2) chromosomal structure, and (3) organization of populations?
How does the Human Genome Diversity Project contribute to
this understanding? Wouldn' t it be possible to carry out this analysis
one population at a time, one chromosomal region at a time: for ex-
ample, for chromosome 12 in western Finland? Of course. This is
analogous to sequencing a part of the genome from one person with
disease at a time. Indeed, this is where we stand right now with the
Human Genome Project. Individual studies are a necessary interim so-
lution. However, much more is to be learned, and the information will
be more universally useful, if disequilibrium structure is studied for
the genome as a whole and in populations with a range of historic fea-
tures. Small numbers of people from many historically coherent pop-
ulations, specifically including those without disease, are the best source
of this information.
Why should anyone from any populationparticularly indige-
nous populations exploited for lifetimes by outsidersbe willing to
1 DO
THE HUM A N GENDM E DI VERSI TY PRDJECT
participate in such research? Good question. A fundamental tenet of
those of us working on the Nort h American Regional Committee of
the HGDP is that any community, including in particular indigenous
communities, should control research access to their own community,
to their DNA, and to any possible commercial value from research
with these resources, however remote the possibility of commercial
value might be.
In our research on breast cancer in families, many families choose
to participate in our project; others decline. Similarly, in the Human
Genome Diversity Project, it is to be expected that some communities
would participate and others decline. It is obvious to me that individ-
uals, families, and communities have the wisdom and intelligence to
make these decisions for themselves, and the right to be provided with
information that is useful for doing so. With these principles in mind,
the Nort h American Committee of the HGDP has developed a draft
of a model ethical protocol for the collection of DNA samples for re-
search. Your committee has, of course, obtained and discussed this
draft protocol. We hope that the HGDP will break new ground in rec-
ognizing the autonomy of communities in making such decisions, and
that this standard will be applied beyond HGDP to biomedical re-
search generally.
9
It was proposed that the information gathered through the HGDP would
help clarify the history of specific populations of the human species as a whole
because the frequencies of different variations in different populations could
reveal how recently they shared a large pool of common ancestors. For exam-
ple, frequencies such as these had potential to be used to see whether, for ex-
ample, the Norwegians are more closely related to the Germans or the Danes.
In addition, it was proposed that the HGDP had potential to yield signifi-
cant information on major human migrationswhere people came from, what
geographical routes they t ook to get to their present territories, and what tech-
nological innovations they used to get there. Ot her information to be derived
would be social interactions within their own group and with other groups,
why and how different traits or languages developed and whether there were
major population reductions due to disease or substandard living conditions.
The project would potentially enable scientists to map the history of civi-
lization.
Certain ethnic groups were brought by different migrations from various
parts of the world and the HGDP proposed to determine whether a single group
was ancestral to all members of a group. Studying genetic variations of peoples
around the world has the potential to provide a great deal of information about
the development of the human species and to help understand relationships be-
tween different populations. In addition, the HGDP proposed to help settle the
long debate about whether Homo sapiens evolved to modern humans in Africa
or over the entire world.
Organizers of the HGDP acknowledged early that variation could be explained
by environmental factors such as climate, pollutants, diet, infectious diseases, and
1 D 1
THE GENETI CS REVDLUTI DN
parasites. However, they also knew that DNA variation was a major contributor.
By studying genetic variations in different populations, particularly those groups
that have lived in isolation for thousands of years, scientists could understand
how humans evolved and migrated over the planet. The study, organizers be-
lieved, had the potential to increase the likelihood of developing effective ways of
treating and preventing diseases.
The HGDP sought to provide answers by leading to a greater understanding
of the differences between individuals and between human populations. The
HGDP promised to make a significant contribution to the elimination of racism
by showing that there is a continual graduation from one population to another
and there is no such thing as a clearly defined race. The HGDP declared the poten-
tial to bring together people from many countries and disciplines. It promised to
create a unique bridge between science and the humanities. Even populations
that do not seek scientific explanations for their origins might reap long-term
benefits from the discovery of useful medical information about their suscepti-
bility to, or treatments for, disease.
Considering Populations
It became apparent to HGDP organizers that not all populations could be studied
in detail. However, scientists were determined that no group would be deliber-
ately excluded. Therefore, it was decided that if certain populations did not wish
to participate in the HGDP they would not be included. To achieve this goal, in
October 1992 a planning workshop for the HGDP proposed examples of popu-
lations that were broadly representative of all major regions of the world. Some
of the proposed populations were small, whereas others were very large. After
much study, approximately 500-800 indigenous representative human world
populations (including those in Europe and Nort h America) were viewed as a po-
tential group to make up the study.
10
Among the indigenous groups suggested for study were peoples of the Sahara,
of western, southern, and eastern Africa;
11
the Etas of Japan, and insular popula-
tions in Malaysia and southeastern Asia.
12
'
13
Other ethnic groups included mi-
norities of China, Polynesians, aboriginal populations of Australia and Melanesia,
the Kurds of eastern Turkey, peoples of the Caucasus, the Lapps, the Basques,
other peoples in the Pyrenees, Appenines, Carpathians, and Alps, and the many
Indigenous American populations.
In addition, the Central Australian Aboriginal Congress (CAAC) reported that
at least a dozen aboriginal communities throughout Australia were proposed to
participate in the project. Among others suggested for DNA sampling were
the Yukaghir of Siberia (about 100 people remaining in the group), the Dorasque
of Panama (50 individuals remaining) and the Amazon' s Akuriyo (50 survivors).
Other communities included the Salsiat of Taiwan, Somalis in the famine-
stricken Horn of Africa, and the Onondagas, the Cayuga, the Delaware, and the
Sarcee of Nort h America (each numbering around 600 persons).
Not all the proposed indigenous communities were thrilled by their inclusion
and asked for an explanation of how populations were selected. The Onondagas
l D2
THE HUM A N GENDM E DI VERSI TY PROJECT
were enraged to find their nation on the list, saying they had not been asked and
wondered why they were named. A second Iroquois nation, the Cayuga, also
made the list and was not happy.
14
Representatives of the HGDP issued a statement staying that populations
that were proposed were done so for historical, genetic, cultural, and other reasons.
Some of the things, they declared, that made a population of particular interest
included an unusual language, culture, or history; an indication of susceptibility
to or immunity from particular diseases and possible extinction; or a possible re-
lationship to another interesting population. The HGDP gave the following
explanation: "One criterion for inclusion was imminent danger of extinction.
This applies to about half of the selected groups, including the Hazda of Tanza-
nia, the Yukaghir of Siberia and the Onge and Greater Andamanese of the An-
daman Islands, Malaysia. Another objective was to choose groups whose genetic
make-up could shed light on specific anthropological problems, such as how the
Americas were first colonized, or the history of the Bantu expansion in Africa
2000 years ago."
15
The small size of the population was another important criterion. Henry
Greely, on behalf of the Nort h American Regional Committee' s Ethics Subcom-
mittee, issued the following statement:
For example, one group in Tierra del Fuego reportedly has only two
members. Should those people die, or, perhaps more likely, move to a
city, sampling may be difficult or impossible. The actual collection of
samples will depend on the willingness of the population to be sam-
pled, as well as on the interest of an anthropologist or other person
knowledgeable in the population' s culture to ensure that the collection
is done in a way that provides true informed consent and that com-
ports with the population' s culture.
16
Because prior research into variations among human populations appeared
to be proceeding in a haphazard and invisible way, Greely and other organizers
felt the HDGP was an effort to coordinate the work and make sure it was done
with the highest scientific and ethical standards.
17
Sampling
In light of equity, it was proposed by HGDP organizers that each region be given
the opportunity to define its own local sampling procedures. It was decided that
questions might be asked about various issues, including human history and
identity that concerned geneticists, anthropologists, and historians. Questions
might be raised by populations themselves which would include genome-wide,
statistical, and locus-specific information. Miscellaneous questions would consti-
tute an important part of the sampling.
In order to preserve history, the HGDP proposed to collect DNA samples from
hundreds of different populations, as well as demographic, historical, sociocultural,
linguistic, and other data from all over the world. This would be in contrast to the
l D3
THE GENETI CS REVDLUTI DN
Human Genome Project, where samples would come mostly from people of Eu-
ropean origin.
It was proposed that the collection and analysis of DNA samples, in con-
junction with the necessary epidemiological data, would lead to the identification
of genetic factors in certain human diseases and eventually to ways to treat or
prevent those diseases. Participating health-care workers would provide some
screening immunization, diagnoses, or treatment of medical conditions while
working with populations, particularly those considered to be on the brink of
near extinction.
It was suggested that in some large linguistic or geographical populations
multiple (rather than single) samples would be taken. DNA samples would be
taken from blood, hair roots, cheek cells, and sputum, as well as other biological
materials. All samples would be collected in culturally appropriate ways, with ex-
plicit informed consent from surveyed subjects. This type of sampling would al-
low communication with the population and allow participants to learn from
findings of the research.
Samples would be frozen and preserved in both central and regional reposi-
tories around the world. Regional laboratories would be set up for processing the
specimens because samples would have a limited time of forty-eight hours to be
processed. One example suggested for a regional repository was the American
Type Culture Collections in Rockville, Maryland. Basic, preliminary analyses of the
DNA samples would be carried out prior to freezing the samples. DNA samples
would be preserved as cell lines in gene banks in order to obtain a large amount of
duplicate DNA for study. These "immortalized cell lines" would be made available
to any qualified scientists worldwide interested in doing legitimate research on
them. Once the DNA samples had been analyzed, the results of the analyses
would be put into a computerized database for distribution worldwide.
Cavalli-Sforza urged that the study be started immediately, warning that if
sampling were delayed, it might be too late for some discrete tribes such as the
Yanomami, who were dying in large numbers from disease and environmental
damage caused by gold mining in the Amazon forests.
18
"It would be tragically
ironic if, during the same decade that biological tools for understanding our
species were created, major opportunities for applying them would be squan-
dered."
19
Unfortunately, what began as a humanitarian and scientific effortto coor-
dinate and ascertain that the HGDP would be carried out only with the highest
integrity and ethical standardswas met with considerable resistance by indige-
nous communities, who were upset with many aspects of the HGDP. Despite at-
tempts to quell the uprising against the project, the debate continued to heat up.
1 D4
V
THE HGDP DEBATE
After being subjected to ethnocide and genocide for 500 years,
which is why we are endangered, the alternative is for our DNA
to be stored and collected . . . why don' t they address the causes
of our being endangered, instead of spending $20 million for five
years to collect and store us in cold laboratories? If this money
will be used instead to provide us basic social services and pro-
mote our rights as Indigenous Peoples, then our biodiversity will
be protected.
Victoria Tauli-Corpuz, Cordillera Peoples'
Alliance, The Phillipines
The Human Genome Diversity Project (HGDP), dubbed the "Vampire Project"
by opponents worldwide, has been enmeshed in substantial controversy since its
beginnings, with intense reactions from many of the indigenous groups it pro-
posed to study. When an article written by Luigi Luca Cavalli-Sforza et al. ap-
peared in the scientific journal Qenomics, various indigenous peoples were
appalled by what they perceived as an insensitive term used by the authors. The
term "isolates of historic interest" was used to describe indigenous peoples pur-
portedly selected for human DNA sampling.
1
Some indigenous groups suggested
the term had the ring of eugenics.
THE GENETI CS REVOLUTI ON
Concerns of Indigenous Peoples
For several decades, indigenous peoples have had concerns of various kinds, so it
was not a complete surprise that they were distressed when it was announced that
a diversity project was planned. Upon the report that the HGDP wished to ob-
tain DNA from the indigenous peoples, that concern intensified and became an
acute issue.
Because of language differences, it was of utmost importance to the HGDP
organizers that the project be understood by the indigenous involved, not merely
presented. In addition to translation problems, however, there was the potential
for differences in ethnic views. In attempts to allay fears of the indigenous peo-
ples, organizers of the HGDP declared openly that it was not their intent to inflict
harm on indigenous peoples. Rather, they said, the project intended to "immor-
talize" endangered populations by establishing viable cell lines in the search for
unique DNA sequences that could offer clues to genetically caused diseases and
to potentially lucrative cures.
HGDP organizers were questioned by conservationists, scientists, and organ-
izations whose primary concern was that the indigenous peoples not be exploited
when obtaining the DNA samples. Indigenous peoples questioned what was in it
for them and repeatedly said they didn' t need scientists or anyone else telling
them where they came from, or, for that matter, where they were going. They
made it quite clear that they had strong beliefs and knowledge about their cre-
ation and histories.
Ray Apodaca of the National Congress of American Indians did not agree
with what he termed the "pure science" justification of the HGDP, particularly
with reference to the history of human migrations, saying: "We know where we
came from, and we know who we are, and we think we know where we are going.
Why do we need to know anything else? I mean, is it for their benefit? It certainly
isn't for ours."
2
Major concerns of indigenous peoples included possible violation of human
rights, biological warfare, informed consent, biopiracy, and diversion of funds.
Other issues surrounding the HGDP had indigenous peoples and support groups
demanding that the project be halted until moral, ethical, socioeconomic, politi-
cal, and physical implications were discussed and agreed upon.
Violation of Human Rights
With regard to possible violation of human rights, the South and Meso Ameri-
can Indian Information Center (SAIIC) from the beginning stated that indige-
nous peoples from whom DNA samples were to be taken had not been consulted
during any planning stage of the project. The SAIIC emphatically argued that in-
digenous peoples from whom samples were to be taken must be given informa-
tion about risks, benefits, and alternative procedures, as well as information as to
how the DNA samples would be used and the purposes of the HGDP research.
Apodaca and others viewed drawing of blood samples as a sacrilege. They re-
minded scientists that obtaining blood samples and other tissues from indigenous
1 D6
THE HGDP DEBATE
peoples was not very different from studies of the last century when hundreds of
Native American graves were robbed and skull sizes taken in a study to estimate
racial intelligence. They cited those studies and others in an attempt to show in-
digenous peoples as victims of inhumane treatment and human rights violations.
This was, they thought, especially true of those studies they believed belittled Na-
tive Americans as being inferior and less intelligent.
Biological Warfare and Ethnic Genes
Some indigenous peoples' groups had concerns about biological warfare, in spite
of HGDP organizers repeatedly stating that the HGDP had no implications for
biological warfare. Because all humans share the same gene pool, specific ethnic
groups are not defined by any specific genes and it seemed, at the time, next to
impossible to create ethnic-specific genes. Quite likely, had this been possible, a
large number of diseases would already have been eliminated. There was, indige-
nous groups stated, always the possibility that with technological advances, some
unethical scientist might gain access to the desired information. Recorded in past
history are cases of oppressed indigenous peoples in various regions of the world
who have been the target of genocide. Uncovering such information would make
it easier for individuals or governments to design and use biological weapons
against populations.
Informed Consent
One of the main concerns of indigenous peoples was the lack of informed con-
sent. They wanted the right to decide, collectively, whether they would partici-
pate in the HGDP. They requested fully informed consent for population
sampling. As a result, the HGDP organizers promised that only those popula-
tions, and individuals within the populations, who consented to the HGDP
would participate.
3
Indigenous peoples raised a large number of ethical questions, including:
How would scientists obtain informed consent from the people under study?
Who would own the resulting stockpile of genetic material? Would the individu-
als giving these samples know what happened to them? Were the donors con-
sulted about further applications to the scientific findings? Were they assured of a
share of any benefits? Who was authorized to give consent? Should consent be
granted by government officials of the nation-state in which the indigenous na-
tion was located? Should consent be required only by the individual being sam-
pled, or also include the governing body of that particular indigenous nation?
Other questions were: How would permission be obtained for collection of
samples from the dead, or for use of fetal and placental tissues as sources for ge-
netic samples? How would the project be explained in the local language? Would
the full scope of the project and the short- and long-term implications and poten-
tial uses of the samples be fully disclosed? Would donors be fully informed of the
potential for profits that may be made from their genetic samples?
4
1 D7
THE GENETI CS REVOLUTI ON
Biopiracy and Diversion of Funds
Indigenous peoples were concerned that DNA specimens would be taken from
indigenous individuals without rewards of any kind. The Rural Advancement
Foundation International (RAFI), an international nongovernmental organiz-
ation, was the most instrumental in aiding indigenous peoples against what they
called "bio-colonialism" or "biopiracy."
RAFI cited earlier cases in which Third World peoples previously provided
biological materials and information without rewards of any kind. They reported
that, repeatedly, western science had been exported to the Third World without
prior consultation with those who were supposed to benefit. Examples included
the wholesale collection of samples of crops and wild plants by foreign scientists,
as well as by drug and chemical companies.
5
Indigenous groups believed that seed and drug companies from the devel-
oped world had long exploited the developing world' s plant genetic resources.
Some companies, it was charged, freely gathered plants from generations of in-
digenous farmers in undeveloped countries. These plants had been developed,
domesticated, and maintained for hundreds of years. Without paying anything to
the farmers or their countries, the pharmaceutical and seed companies used the
plants to create products that were then patented and sold back to the developing
world at high prices for high profits. Few, if any, of the profits, some indigenous
groups believed, were returned to the patents' original users. The exploitation of
the plant and animal genetic resources of the developing world played a major
role in the 1992 Biodiversity Treaty.
Advocates for indigenous peoples were concerned that the HGDP would be
a human version of these plant-collecting expeditions. Emphatically, the HGDP
promised that this would not happen. It also declared that it was committed to
two propositions: first, that financial benefits should not go to the HGDP; and,
second, that an adequate part of the financial gains, if any, would go back to the
sampled populations.
Unconvinced, RAFI cited another incident that had occurred on the small is-
land of Tristan da Cunha in the South Pacific. In 1991 two researchers from the
Mount Sinai Hospital in Toronto, Ontario, had visited the island, interested in
researching residents with a high incidence of hereditary asthma. While on site,
the researchers allegedly took blood samples from 272 of the island's 295 inhabi-
tants.
Shortly after the researchers returned to Toronto it was announced that
Mount Sinai Hospital had formed a contract with Sequana Therapeutics, a
biotechnology company that was to analyze the blood samples in attempts to
identify the asthma gene. The contract stipulated that any patent profits would be
shared by Sequana and the hospital, bypassing the island's citizens who had actu-
ally donated the blood. The contract included potential profits made from
patenting human genes (particularly to large pharmaceutical companies) and di-
version of any funds generated.
6
Citing other such cases, indigenous peoples worried that their most funda-
mental property (their own DNA and genes) would end up in the hands of almost
anyone who wanted to experiment with them. Indigenous peoples argued that,
l as
THE HGDP DEBATE
like other companies in the past, the HGDP potentially could amount to wide-
spread commercialization and potential misuse of samples and data.
In defense of their study, organizers of the HGDP once again tried to as-
sure the indigenous communities that the HGDP was not intended to be a com-
mercial venture. Rather than profit, it sought knowledge. In September 1993,
at its international congress, the HGDP formally announced that it would
not profit from the DNA samples or data developed from the samples. How-
ever, in the event that it evolved into profit, the HGDP was committed to
ensuring that any financial benefits would be given back to the donor popula-
tions.
The HGDP also said it did not intend to patent DNA samples taken from in-
digenous peoples or any products made from the samples. However, the World
Congress of Indigenous Peoples (WCIP) and RAFI each said that they believed
that the HGDP was motivated by the potential to make profits from medical re-
search more than by the pursuit of knowledge.
George Annas, Professor of Medical Ethics at the Massachusetts Institute of
Technology, issued a similar concern: "We' re taking from them their DNA,
which we now consider like gold. It's even worse than standard colonialism and
exploitation because we are taking the one thing that we value. And after we take
that we have no real interest in whether they live or die. We need to secure their
future as peoples, not just immortalize their genes."
7
Patents and Indigenous Peoples
In the United States, numerous patents had been issued by the U.S. Patent and
Trademark Office (PTO) on created living animals, microorganisms, and human
genes and tissues, breaking the long-standing policy that animate life forms were
not patentable. In 1971 the General Electric Corporation and one of its scientists,
Ananda Chakrabarty, filed a patent application for bacteria which could digest oil
hydrocarbons. In determining whether to award the patent, whether it was alive
or inanimate was seen as the major criterion. Initially, the US. Patent Office re-
jected the application. However, the case was appealed to the courts and in 1980
the Supreme Court ruled, in a five to four opinion by Chief Justice Warren
Burger, that the oil-eating microbe was not a product of nature but a human-
made invention.
In 1987 the U.S. Patent Office decided that all multicellular living organisms,
including animals, were held patentable. Since that time, the National Institutes
of Health (NIH) has secured patent rights for fragmented gene sequences, allow-
ing corporations and research institutions the right to secure patents on a sub-
stantial percentage of the entire human genome.
The issue of patents on genetic samples obtained from indigenous peoples
became a controversial subject and resulted in a heated written exchange between
Henry Greely of the HGDP and Edward Hammond and others of RAFI. Report-
edly, NIH patent claims on indigenous peoples' DNA were undertaken by the
National Technical Information Service, a division of the U.S. Department of
Commerce.
8
l D9
THE GENETI CS REVDLUTI DN
The Guaymi Patent
In 1993 U.S. Secretary of Commerce Ron Brown filed U.S. and world patent
claims on a cell line of a twenty-six-year-old Guaymi woman from Panama. The
cell line was of particular interest because it was known that some Guaymi peo-
ple carried a unique virus in their cell lines and the antibodies to that particular
virus were thought to be useful in AIDS and leukemia research. However, the
Guaymi people viewed the patenting of humans and animals as fundamentally
immoral and contrary to the Guaymi view of nature and their place in it. Because
of their beliefs, the President of Guaymi, on behalf of his people, cited the patent
as a violation of the integrity of life itself.
Although the patent application had nothing to do with the HGDP, Henry
Greely attempted to explain the American Type Culture Collections cell line
patent in a July 21, 1993, letter to Pat Roy Mooney of RAFI:
I have now talked with Dr. Michael Lairmore and have found out
some more about the ATCC cell line you brought to my attention. I' m
not sure what to make of that information, but I pass it along to you
for your consideration.
An NIH researcher working at the Gorgas Institute in Panama no-
ticed that blood from a large percentage of a certain population in
Panama showed some antibodies. He sent a sample to CDC for identifi-
cation of the virus that had triggered the antibodies. It ended up with
Lairmore [Dr. Michael Lairmore], who was then a CDC virologist. He
and his colleagues discovered that the antibodies were being formed to
the HTLV-II virus. This virus is closely related to the HTLV-I virus,
which is known to cause some neurological and other symptoms and is
common in the Caribbean and in American intravenous drug-using
populations. HTLV-II has not been linked to any diseases or conditions.
At CDC, they managed to create a cell-line from the same blood
cells. That cell-line perpetually produced HTLV-II virus. They created
the cell-line for the use of researchers interested in HTLV-II virus.
Someone at CDC then told Lairmore that he should patent the cell-
line, so he and his colleague called the CDC' s patent office and they
put the process in motion. He doesn' t know the financial side of the
patent but assumes the federal government owns the patent and would
be in a position to get any financial returns with perhaps a nominal
sum going to the "inventors" (who were both government employees).
All the interest in the cell-line, both scientific and, perhaps, commer-
cial, has focused on the production of the virus by the cells. No one, as
far as Lairmore knows, has paid any attention at all to the human gene-
tic information in the cell line.
As far as Lairmore knows, the patent has not been issued. He
doesn' t have much interest in it. It might conceivably become valuable
as the source of a screening test for HTLV-II virus infection. However,
that potential value has three drawbacks. First, right now it isn't known
that HTLV-II virus infection causes any symptoms that anyone would
l 1 D
THE HGDP DEBATE
want to screen against. Second, many other populations with endemic
HTLV-II virus have now been found and they could just as easily be
used to produce cell-lines that produced the virus. And third, the en-
tire genetic sequence of that virus has now been determined, using
that cell-line, and is about to be published in the August issue of the
Journal of Virology (lead author, Diane Pardi). Now that the sequence
(about 9,500 base pairs) is known, a source of the actual virus is prob-
ably less important for any commercial purpose.
So, this is an example of a cell-line from a member of an indige-
nous group for which a patent has been sought. It does not seem to
have a significant chance of having any commercial value, although
that can' t be ruled out. And it is not the human genes that are of any
interest. Still, this does point out another way in which cell-lines have
economic value and one I hadn' t thought of. I agree we need to think
harder about the economic value issues and I am still interested in
your thoughts on an appropriate "fund-holder" for any royalties that
might come in. I look forward to hearing from you.
9
The patent application was first discovered in August 1993. Pat Mooney of
RAFI was examining a patent database primarily for agricultural information
when he came across the application filed by United States Secretary of Com-
merce Ron Brown on the cell line of the twenty-six-year-old Guaymi Indian
woman from Panama. Mooney, on behalf of RAFI, immediately contacted the
Guaymi General Congress in Panama City about the patent claims. He also
alerted the US. Biotechnology Working Group, a group of international activists
who had gathered in Geneva at the time. Very concerned, RAFI and others made
known their beliefs that such patenting was a very dangerous trend toward com-
modification of humanity, whether it was by taking DNA samples from indigenous
peoples or medicinal plants. RAFI requested that the United States withdraw its
patent claims and return the cell line to the Guaymi people.
In early October that same year, Mooney, representing RAFI, and the
Guaymi president traveled to Geneva to protest the U.S. Guaymi patent claim at
the intergovernmental meeting of the Biodiversity Convention, held October
10-15, and to the General Agreement of Tariffs and Trade (GATT) Secretariat.
Isidro Acosta, President of the Guaymi General Congress, and Jean Christie
of RAFI met with the GATT Trade Related Intellectual Property Rights Secre-
tariat, and after much discussion, determined that human genetic material was
not excluded from the GATT agreement. Intellectual property clauses of the
GATT agreement required states to adopt patent laws covering microorganisms
and (some form of protection for) plants. International precedentunder the Bu-
dapest Conventionled to the treatment of human cell lines as nothing more
than a form of microorganismin the same class as fungi, bacteria, or viruses. In
so doing, the GATT mandated the patenting of human material.
Later in October 1993, the European Greens introduced an emergency reso-
lution into the European Parliament. Opposing the patent claims, they requested
data on European patenting and called for a halt of the HGDP. Subsequent inter-
national protest and action by the Guaymi General Congress, RAFI, the World
1 l l
THE GENETI CS REVDLUTI DN
Council of Churches, the World Council of Indigenous Peoples (WCIP), and in-
dividuals, including Henry Greely of the Nort h American Subcommittee of the
HGDP, resulted in the withdrawal in November 1993 of the patent claims by the
U.S. secretary of commerce.
10
On November 9, 1993, Nilo Cayuqueo, SAIIC Director, sent a fax to Henry
Greely as chair of the Ethics Subcommittee of the Nort h American Regional
Committee:
We have an array of serious concerns that, to date, have not been ad-
dressed at all:
(1) The information you gather about our genetic make-up will be
readily available to governments, foundations, and corporations. For
the past 500 years, these institutions have waged an unbridled war of
oppression and genocide against our people. The implications are
potentially devastating for Indigenous Peoples all over the world.
How are we going to be able to control these institutions from
patenting and thereby owning the rights to our genetic material en-
abling them to make profits from our own blood? What kind of reg-
ulations are going to be set to ensure that this information is not
going to be used against us in targeted biological warfare?
(2) In your statement to us you say, "The populations that will be
studied will be populations that choose to participate (and those in-
dividuals within the populations that also choose to participate)."
How will the targeted populations be approached? How will the
project be presented to them? What kinds of methods and tactics
are going to be used to convince the communities that by "donating
blood" they will benefit in some way? Given the history of the past
500 years, where and how does choice factor in?
(3) The notion that the Guaymi sister in Panama "donated her blood"
indicates the narrow and paternalistic way in which the people in-
volved regard the situation. It is still not clear how she was ap-
proached and why the President of the Guaymi General Congress,
Isidro Acosta, was not involved from the onset. To imply that the
woman would have willingly given her blood sample had she known
the U.S. government was going to then apply for a patent on her
cell-line is ludicrous. Your description does not reflect the reality of
the situation, Mr. Greely, and this is very dangerous.
(4) The targeted Indigenous Communities have been referred to as
"Isolates of Historic Interest." Due to the relentless oppression of
the past 500 years, many of our peoples have been the victims of
genocide and marginalization, our populations have dramatically
decreased in size as our land has been overtaken and our way of life,
our culture, our traditions totally overshadowed by the dominant
capitalist mind set. In spite of this, we have endured and are 45 million
strong in the Western hemisphere. Lest you think we are vanishing,
l l 2
THE HGDP DEBATE
we are not. We are living here and now under deplorable conditions
imposed upon us by the oppressive government regimes that try as
they may have not succeeded in exterminating us.
With all the money and effort that is going to be expended to try
to further exploit us, we believe the time, energy and money could be
better put to much better use by: helping our communities in our
struggle for self-determination; getting governments to acknowledge
our way of life; honor broken treaties and allow us to reclaim our
rightful territories; stopping the human rights violations against our
people and our land; bringing proper sanitation and medical care to
our impoverished communities; stopping the multinational corpora-
tions from exploiting and destroying our natural resources on which
we all depend.
We would like to make it clear, Mr. Greely, that we do not want to
stand in the way of research that will be to the benefit of all humanity.
However, we will not take part in any effort of the Human Genome
Diversity Project until all of the moral, ethical, socioeconomic, physi-
cal and political implications have been thoroughly discussed, under-
stood and approved by Indigenous Peoples. We do not want so called
"experts" to come into our communities to try and convince us that
for the sake of science we must allow the Human Genome Diversity
Project to do whatever it wills.
What we seek is open dialogue. Until this is granted, we will do
everything we can to inform member organizations to refuse to coop-
erate with the project. We hope that our concerns will be addressed
and that you will do whatever you can to ensure that respect guides
your route.
11
In December 1993, Henry Greely, representing the HGDP, was invited to the
World Council on Indigenous Peoples (WCIP) meeting, held in Guatemala. After
several hours of intensive discussion, the WCIP unanimously voted to adopt a
resolution to halt HGDP. Subsequently, it was discovered that two other patent
claims had been filed by the U.S. Secretary of Commerce for cell lines of indige-
nous peoples, one claim from the Solomon Islands and the other from Papua
New Guinea.
Solomon Islands Patent
After discovering the patent for a cell line from residents of the Solomon Is-
lands, the Solomon Islands government demanded withdrawal of the patent
applications and repatriation of the genetic samples, citing an invasion of sover-
eignty, lack of informed consent, and moral grounds as the reasons for protest.
However, U.S. Secretary of Commerce Ron Brown rejected the requested with-
drawal, saying: "Under our laws, as well as those of many other countries, sub-
ject matter relating to human cells is patentable and there is no provision for
l 1 3
THE GENETI CS REVDLUTI DN
considerations relating to the source of the cells that may be the subject of a
patent application."
12
In September 1994 Dr. Jonathon Friedlaender, Physical Anthropology Pro-
gram Director at the NIH, at the request of the Solomon Islands' ambassador to
the United Nations, investigated the Solomon Islands patent application and ad-
vised the Solomon Islands government that both the Papua New Guinea and
Solomon Islands patent applications would be either abandoned, withdrawn, or
disallowed. However, it was later discovered the Papua New Guinea patent had
been issued in March 1995.
13
Greely issued a press release on October 26, 1995:
In response to 1993 investigations by the Government of the Solomon
Islands and RAFI, NIH' s Jonathan Friedlaender wrote to the Solo-
mon Islands Ambassador to the United Nations, allaying their con-
cerns by saying that the patent applications "will likely be abandoned
entirely or not allowed." Contrary to Friedlaender's indication, in the
course of routine research prior to (Jean) Christie's trip to the Pacific
RAFI discovered that the patent was issued 6 months ago. Friedlaen-
der, who wrote that the patent would likely be withdrawn, participated
in the development of the HGDP and was among those at its founding
meeting. Within weeks of the patent' s issue, Friedlaender returned to
the Pacific on business related to the collection of blood samples.
14
In further defense of Friedlaender, Greely wrote:
The similar patent application for cell-lines derived from the blood
samples from the Solomon Islands was not prosecuted by the U.S.
Government. It was "continued," which means "put on the back
burner," last spring, and I am told that it has now been formally with-
drawn. Dr. Friedlaender's letter to the Ambassador from the Solomon
Islands was entirely accurate about the Solomon Islands application. It
would also have been accurate about the [Papua New Guinea] PNG ap-
plication, except that it did not foresee the strong request from the
PNG Institute of Medical Research that the patent application from
Papua New Guinea be prosecuted.
15
Friedlaender, who was also a tenured professor of anthropology at Temple
University, said he had visited Papua New Guinea and the Solomon Islands after
his stint with the NIH but said that he did not collect any blood samples. He did,
however, admit to collecting various tissue samples for his academic research at
the university.
Papua New Guinea Patent
On March 14, 1995, the U.S. government, in an unprecedented move, issued to
a group of five inventors U.S. patent number 5,397,696, called Papua New
1 1 4
THE HGDP DEBATE
Guinea Human T-Lymphotropic Virus. The patent was on a cell line taken from
an indigenous man of the Hagahai people from New Guinea' s remote highlands.
At the time, the Hagahai numbered a scant 260 persons. They had come into con-
sistent contact with the outside world beginning in 1984. The cell line reportedly
contained the virus variant called HTLV-1, and patent applications on the cell
line were reported to be pending in nineteen other countries.
16
The team that patented the HTLV-1 virus variant was headed by 1976 Nobel
laureate in medicine, Dr. D. Carleton Gajdusek, and Dr. Carol Jenkins, a U.S. cit-
izen and widely respected medical anthropologist. The patent claimed as its "in-
vention" the cell line, viral preparations made from the cell line, and bioassays
made from the cell line. The patent did not make any ownership claims to that
particular human DNA or to the information it contained.
17
RAFI was highly critical of the patent. Edward Hammond, Program Officer
with RAFI-USA, located in Nort h Carolina, issued the statement: "The thin ve-
neer of the HGDP as an academic, non-commercial exercise has been shattered
by the U.S. government patenting an indigenous person from New Guinea."
18
The patent did not give the U.S. government (or anyone else) any intellectual
property rights on the DNA of any member of the Hagahai, although it did give
the patentees exclusive commercial rights (in the United States) to one particular
kind of cell line infected with a particular variant of a virus called HTLV-1 and on
the possible uses of that cell line in developing diagnostic tests. No claim was
made on any human genetic material.
19
Opponents of the patent argued that the Hagahai man' s physical identity had
been patented by the NIH. They argued that the patent, in claiming the cell line,
also claimed the cell's contentsthe viral strain and the human DNA derived
from blood taken from the Hagahai man. Opponents asserted that the patent
claimed a cell line containing the unmodified Hagahai DNA and several methods
for its use in detecting HTLV-1-related retroviruses and in developing vaccines.
As a result of the opposition to the patent, the NIH withdrew its application
to patent the cell line. However, at the request of members of the Institute of
Medical Research, an independent government institute in Papua New Guinea,
NIH changed its decision.
In an attempt to explain what was developing into a fiasco, on Friday, Octo-
ber 20, 1995, Henry Greely wrote:
First, the NIH had decided to withdraw its application to patent the
cell-line derived from blood from Papua New Guinea. The NIH
changed its decision at the request of members of the Institute of
Medical Research, an agency of the government of Papua, New Guinea.
An Institute scientist is listed as a co-inventor on the patent applica-
tion and, by agreement, her half of any proceeds from the patent are to
go to the Hagahainot to the co-inventor, the Institute, or the general
government of Papua New Guinea. (The agreement is not part of the
patent because patents do not include information on the distribution
of the royalties they producethey just describe the protected "in-
vention".) The Institute and its staff have sterling reputations for ser-
vice to the peoples of their country; this patent was issued as part of
l l 5
THE GENETI CS REVDLUTI DN
their service to the Hagahai. The Institute believed that it could best
protect the interests of the Hagahai by a patent. That may or may not
have been correct, but it certainly was not exploitation of the Haga-
haiquite the contrary.
20
The Institute scientist who was coinventor on the patent application,
Dr. Carol Jenkins, offered to donate her half of any proceeds from the patent to
the Hagahai peoples themselves, not to the Institute or the general government of
Papua, New Guinea.
The Institute of Medical Research, with a sterling reputation internationally,
believed it could best protect the interests of the Hagahai people by a patent.
The Institute of Medical Research is considered an exemplary organiz-
ation and the Papua New Guinea government has been extremely wise
to support it. Their staff is internationalmeaning Australian, Ameri-
can, African, Indian, and Papua New Guinean, among othersand they
have an outstanding record of biomedical research achievement and
public health education. A few examples include the identification and
cure of a formerly widespread and lethal disease ("pigbel"), very impor-
tant malaria research, ongoing and important public health education
efforts in nutrition, tuberculosis, AIDS, and ecological degradation.
21
Others who had been following the Papua New Guinea case issued statements,
explaining what they termed "commodification of life." Some Americans, includ-
ing Jeff Keohane of Stanford University, referred to taking genetic material from
the Hagahai man from Papua New Guinea as "commodification": "That person' s
genes were commodified the instant they left his or her body and someone was
willing to spend money for them. The NIH was granted a patent on a derivative of
that material. It doesn' t own anything within the person' s skin. It doesn' t own the
person. It doesn' t have any claim to so much as the sweat in their footprints."
22
Pat Roy Mooney, RAFI' s executive director, issued the following statement:
"This patent is another major step down the road to the commodifcation of life.
In the days of colonialism, researchers went after Indigenous People's resources
and studied their social organizations and customs. But now, in biocolonial times,
they are going after the people themselves."
23
Once again defending the HGDP, Greely responded on Friday, October 20,
1995:
As a member of the North American Committee of the Human
Genome Diversity Program, I share RAFI's concern about the patenting
of a cell-line derived from a member of the Hagahai population, or from
anyone else, indigenous or non-indigenous, who may not have given
fully informed consent to such use of his tissues or who may otherwise
have been treated unfairly. But I am also concerned that the Human Di-
versity Project not be treated unfairly by RAFI. Its press release [Wednes-
day, October 4, 1995] contained such a host of misrepresentations and
outright lies about that Project that I am compelled to respond.
1 l 6
THE HGDP DEBATE
Fact 1. The HGDP had nothing to do with the collection, analysis, or
patenting of the cell line from Papua, New Guinea or with patenting
of any other cell lines, indigenous or otherwise.
Fact 2. The HGDP is a regionally organized project. In most of the
world, including the Pacific and the Americas, it remains entirely in
the planning stage. In Europe and China, local researchers are en-
gaged in pilot studies that might end up being part of the Project.
Fact 3. The HGDP has stated, over and over, (a) that the Project will
not try to capture for itself any commercial value that its samples or
data may generate, through patenting or in any other methods, (b)
but that should such value arise, the Project will seek to ensure that
the sampled population gets a fair share of any benefits.
Fact 4. The Nort h American Committee of the HGDP has gone far-
ther and stated that no patenting or commercial use of samples col-
lected by the Project should be allowed without the express and
informed agreement of the sampled population, provided by what-
ever authorities are appropriate within its culture. We expressly re-
ject unfair and exploitative "gene hunting."
Fact 5. The HGDP has not supported the U.S. government patent ap-
plications on cell lines from Indigenous Peoples. In fact, I personally
helped the Guaymi General Congress and RAFI persuade the NIH
to drop its patent application on a cell line from Panama. I discov-
ered the nature of the patent application, the named inventors on
the application, and the background of the patent and passed that
information on to RAFI, which didn' t know any of it. I wrote to
and talked with the relevant federal officials in the efforts that led to
the withdrawal of the Guaymi claim. I also offered to help the gov-
ernment of the Solomon Islands in the same manner.
Fact 6. There is not, and never has been, an HGDP list of populations
to be sampled. In October 1992, a planning workshop for the
HGDP created a set of tables showing examples of the kinds of pop-
ulations that would be of particular interest for studying the genetic
diversity, and hence the genetic history, of humanity. The HGDP
gave a draft copy of those tables to RAFI, which has proceeded for
several years to refer to them as showing "targeted populations" and
now as being "a hit list." As we have told RAFI often, these drafts
were never completed and the idea of even discussing specific popu-
lations as examples was abandoned more than two years ago be-
cause of the way it was being misunderstood.
Fact 7. When Edward Hammond of RAFI says, "The thin veneer of
the HGDP as an academic, non-commercial exercise has been shat-
tered by the U.S. government patenting an indigenous person from
Papua New Guinea," he is, to be most charitable, grossly misin-
formed. The HGDP Project is NOT the United States government.
It is an international effort by scholars from around the world to
i l v
THE GENETI CS REVDLUTI DN
increase our understanding of our common human heritage. Al-
though several years ago, it received minor federal funding for plan-
ning workshops, it has no current funding from the United States
government. It hopes to get federal funding, but even then I am sure it
would not accept funding that required the samples to be patentable
without the informed consent of the populations involved.
24
The debate intensified and RAFI moved to take the life patenting issue to the
World Court at the Hague as well as to the Biodiversity Convention and relevant
multilateral bodies. RAFI had been monitoring the patenting of indigenous peo-
ples since 1993 when the patent was applied for (and subsequently withdrawn) by
t hen-US. Secretary of Commerce Ron Brown on a cell line from the Guaymi
woman.
On October 2, RAFI' s Jean Christie was in Port Moresby and telephoned
Dr. Carol Jenkins at the Institute of Medical Research to discuss the patent. On
her return from Honiara and Port Moresby, Christie issued a statement: "This
outrageous patent has provoked anger in the Pacific and is a matter of deep con-
cern worldwide."
25
Expressing belief that the HGDP was motivated to make profits on patenting
genetic materials, in a newsletter of the Australian GenEthics Network, The Qene
Report, Christie wrote that she believed that any money spent on collecting DNA
samples from threatened indigenous peoples should be used to help these people
to survive and improve their living conditions.
The profit potential in indigenous germ plasm was brought home to
drug companies this year when 30 people in the isolated Italian town
of Limone were found to have a unique gene that codes against many
cardiovascular diseases. Swedish and Swiss companies and the Uni-
versity of Milan have applied for patents. If the gene produces a mar-
ketable therapy, big profits are likely. Such patents may outlive the
indigenous peoples from whose hair, blood and guts they are drawn.
The National Institutes of Health (NIH) has already applied to patent
more than 2800 genes and DNA fragments from the Human Genome
Project's study of brain tissue, and HUGO teams in England and
Japan plan to file for patents.
26
Other groups stepped in and voiced opposition to the HGDP. Alan Swed-
lund, head of the Anthropology Department at the University of Massachusetts,
earlier announced that an increasing number of anthropologists were opposed to
the HGDP because they felt there was a decline in social and cultural issues and
an increase in genetic determinism. Swedlund said that HGDP managers "have
hitherto ignored the plight of aboriginal peoples but now want to swoop in, col-
lect blood for their own scientific goals, and then leave people to their fate."
27
Edward Tilton, project officer for the Central Australian Aboriginal Con-
gress (CAAC), issued the following statement: "The HGDP is immoral and has
no beneficial purpose to the Aboriginal peoples in the sense that it's just treating
people as mere sources of genetic information. Aboriginal people will have no
l l B
THE HGDP DEBATE
control over these samples, which will be frozen someplace in the United States
where they'll be kept for decades, even centuries. So people won' t have any con-
trol over how their genes are used. It's very much a continuation of the research
on people rather than the research with people approach."
28
The HGDP responded that genocidal use of genetics was not possible with
what was then current technology and, further, based on what they knew of hu-
man genetic variation, it seemed impossible that it would ever be developed. The
HGDP condemned and barred any effort to use its data for such purposes. The
best ways to implement those commitments depended on some complex issues
of patent and contract law that had not been entirely resolved at the time, as well
as on some decisions by the sampled populations or their representatives on how
best to proceed.
The HGDP declared its plans to implement their decisions after consultation
with representatives. The commitments they made promised to be firm. Once
again, the HGDP promised that it would not profit from any samples obtained
from indigenous peoples and that it would do its best to make sure the financial
profits, if any, were returned to the sampled populations.
Calls for a Halt
The HGDP was heavily criticized by various indigenous groups, as well as by an-
thropologists, geneticists, and psychologists. Leonora Zalabata, spokeswoman
for the Arhuaco people of northern Columbia, was particularly wary of the
HGDP and its possible exploitation, saying: "Our land, our culture, our sub-soil,
our ideology and our traditions have all been exploited. This could be another
form of exploitation, only this time they are using us as raw materials."
29
As early as May 1993 RAFI had begun to sound an alarm about potential
abuses and commercialization of human genetic material. At that time RAFI
made accusations that the HGDP was planning to collect and "immortalize" hu-
man tissue from 722 human populations (10,000-15,000 actual persons) which
included indigenous peoples around the world. RAFI made known its objections
to the HGDP when it notified the World Council of Indigenous Peoples (WCIP),
the First International Conference on the Intellectual and Cultural Property
Rights of Indigenous Peoples, and other Indigenous Organizations.
Chief Leon Shenandoah, of the Council of Chiefs of the Onondaga Nation,
believing that the HGDP was violating human rights of indigenous peoples, sent
the following message to the National Science Foundation: "Your process is un-
ethical, invasive and may even be criminal. It violates the group rights and human
rights of our peoples and Indigenous Peoples around the world. Your project in-
volves the very genetic structures of our beings."
30
In June 1993, the WCIP and RAFI raised pointed questions about HGDP at
the United Nations Human Rights Conference in Vienna and asked for a halt of
the HGDP until the project could be further studied. This was followed by
RAFI' s discovery in August that the U.S. government had applied for U.S. and
world patents on the cell line of the twenty-six-year-old Guaymi Indian woman
from Panama.
1 1 9
THE GENETI CS REVDLUTI DN
On Thursday, November 4, 1993, Henry Greely received an e-mail from Pat
Roy Mooney, the Executive Director of RAFI, in which Mooney stated:
We still believe that the Human Genome Diversity Project must be ap-
proved by Indigenous Peoples' organizations and must function under
the auspices of the United Nations. We continue to be concerned that
commercial benefits could arise from the Project and that they may
not be shared equitably. We are justifiably concerned that intellectual
property rights might be applied related (directly or indirectly) to hu-
man cell lines collected under the Project. We are further concerned
that the information acquired could lead to further discrimination
against Indigenous Peoples or even be used for population-targeted bi-
ological weapons.
31
The Third World Network received information from RAFI that U.S.
HGDP scientists had started to collect human DNA samples from indigenous
communities throughout the world. Subsequently, there was a call by indige-
nous peoples' groups to mobilize public opinion against the case of human com-
munities as material for scientific experimentation and patenting. The SAIIC
asked that representatives of the HGDP hold a meeting with the World Indige-
nous Council so that fair and open dialogue could take place and the peoples
involved would be able to voice their needs and perspectives as active partici-
pants.
32
Various indigenous groups around the world called for an immediate halt of
the HGDP and its activities. The groups made known to the world that they had
a right to be recognized as fully human communities with full human rights, in-
cluding the right to decide how other countries related to them. Indigenous
groups were asked to write or call President Clinton, the U.S. National Institute
of Health, and respective indigenous governments to demand that the U.S. gov-
ernment withdraw its support of the HGDP.
The South and Meso American Indian Information Center (SAIIC) on Octo-
ber 20, 1993, sent out a memo requesting immediate halt of the HGDP, quoting a
statement of RAFI: "The sampling of human genetics for scientific research has
serious implications for Indigenous Peoples."
33
At the Beijing Women' s Conference, Sami indigenous women from the
Nordic countries added their voices to those organizations that denounced the
HGDP as a violation of their rights.
34
On December 10, 1993, the World Council of Indigenous Peoples (WCIP),
with headquarters in Ottawa, Ontario, issued the following resolution:
Resolution of World Council of Indigenous Peoples (WCIP)
Considering the preliminary discussions undertaken with the Human
Genome Diversity Project;
Considering the presentation of the Chairperson of the Ethics Panel
of the Nort h American Region of the Human Genome Project to
l 2 D
THE HGDP DEBATE
this the VII International Conference of Indigenous Peoples on
08.12.93;
Recognizing the reaction to this Conference to that presentation;
WE RESOLVE TO CATEGORICALLY REJECT AND CONDEMN
THE HUMAN GENOME DIVERSITY PROJECT AS IT APPLIES
TO OUR RIGHTS, LIVES AND DIGNITY.
We also resolve to monitor, follow up and, if necessary, to take action
against this project in all its manifestations, and to encourage Indige-
nous Peoples worldwide to do the same;
Based on the aforementioned, we as representatives of Indigenous
Peoples in the WCIP, are required to inform our Peoples, as a preven-
tative measure, about the Project for the Study of the Diversity of the
Human Genome.
In the event that we become aware of the carrying out of this Project
despite the rejection by Indigenous Peoples, we will go to the respec-
tive international human rights entities to ask for justice in this case.
35
The WCIP Resolution was followed by a declaration on February 19, 1995, by the
Indigenous Peoples of the Western Hemisphere:
Declaration of Indigenous Peoples
of the Western Hemisphere
We are the original peoples of the Western hemisphere of the con-
tinents of North, Central, and South America. Our principles are
based upon our profound belief in the sacredness of all creation, both
animate and inanimate. We live in a reciprocal relationship with all life
in this divine and natural order.
Our responsibility as Indigenous Peoples is to insure the continu-
ity of the natural order of all life is maintained for generations to come.
We have a responsibility to speak for all life forms and to defend
the integrity of the natural order.
In carrying out these responsibilities we insure that all life in its
natural process and diversity continues in a reciprocal relationship
with us.
We hold precious all life in its natural form. The harmonious pro-
gress of the natural order in the environment shapes and defines
healthy genetic diversity.
The principle of harmony requires that we do not violate the prin-
ciples of Creation by manipulating and changing the natural order.
Given that our natural relationship has been interfered with by
foreign or non-indigenous external forces in a long history of destruc-
tion we have never abandoned those responsibilities.
1 2 1
THE GENETI CS REVDLUTI DN
In the long history of destruction which has accompanied western
colonization we have come to realize that the agenda of the non in-
digenous forces has been to appropriate and manipulate the natural
order for the purposes of profit, power, and control.
To negate the complexity of any life form by isolating and reduc-
ing it to its minute parts, western science and technologies diminished
its identity as a precious and unique life form, and alters its relation-
ship to the natural order.
Genetic technologies which manipulate and change the fundamen-
tal core and identity of any life form is an absolute violation of these
principles, and creates the potential for unpredictable and therefore
dangerous consequence.
Therefore, we the Indigenous Peoples and Organizations partici-
pating in this meeting from Nort h, Central, and South America reject
all programs involving genetic technology.
We particularly oppose the Human Genome Diversity Project
which intends to collect and make available our genetic materials which
may be used for commercial, scientific, and military purposes.
We oppose the patenting of all natural genetic materials. We hold
that life cannot be bought, owned, sold, discovered, or patented, even
in its smallest form.
We denounce and identify the instruments of intellectual prop-
erty rights, patent law, and apparatus of informed consent as tools of
legalized western deception and theft.
We denounce all instruments of economic apparatus such as
NAFTA, GATT, and the World Trade Organization (WTO) which con-
tinue to exploit people and natural resources to profit powerful cor-
porations, assisted by governments and military forces of developed
countries.
We demand that scientific endeavors and resources be prioritized
to support and improve social, economic, and environmental condi-
tions of Indigenous Peoples in the environments, thereby improving
health conditions and raising the overall quality of life.
We reaffirm that Indigenous peoples have the fundamental rights
to deny access to, refuse to participate in, or to allow removal or ap-
propriation by external scientific projects of any genetic materials.
We demand the Human Genome Diversity Project and any other
scientific projects cease any attempts to seduce or coerce participation
in their project through promises of benefits and financial gain in or-
der to obtain consent and participation of Indigenous Peoples.
We demand an immediate moratorium on collections and/or
patenting of genetic materials from Indigenous persons and communi-
ties by any scientific project, health organization, governments, inde-
pendent agencies, or individual researchers.
We demand that nation-state governments and their departments
do not participate, fund, or provide any assistance to the Human
Genome Diversity Project or any related programs or seek to hold
1 2 2
THE HGDP DEBATE
patents or otherwise benefit from the genetic materials taken from In-
digenous Peoples.
We call on religious communities, human rights, social justice and
environmental organizations, funding agencies, all individuals, and in-
stitutions to refuse to participate, fund, or provide other assistance to
the Human Genome Diversity Project and any related programs.
We extend our support and solidarity to all those who are resist-
ing these efforts, or are seeking the repatriation of genetic materials al-
ready taken or removed from their control.
We urge the international community and the United Nations to
participate with Indigenous Peoples in developing international poli-
cies and conventions which protect all life forms from genetic manipu-
lation and destruction.
We call on our brothers and sisters of the indigenous nations
around the world and concerned peoples in the international commu-
nity to stand up and unite in our efforts to protect the natural diver-
sity and integrity of all life.
The support of all humans in this Declaration would protect the
sacredness of all life, the natural order, and would provide a healthy
future for generations to come.
As declared by the undersigned participating organizations in
Phoenix, Arizona on February 19, 1995:
Amazanga Institute, Provincial de Pastaza, Ecuador
Association Kunas Unidos Pro Napguana, Panama
Coorinadora de Mujeres Indigenous de Bolivia, Las Pas, Bolivia
CONIC Consortium, Albuquerque, New Mexico
Council of Athabaskan Tribal Governments, Stevens Village, Alaska
En' owkin Center, Penticton, British Columbia, Canada
Independent Traditional Seminole Nation of Florida, Immokalle,
Florida
Indigenous Environmental Network, National Office, Bemidji,
Minnesota
Indigenous Environmental Network, Oklahoma Region, Tulsa,
Oklahoma
Indigenous People's Alliance, Phoenix, Arizona
Indigenous Peoples Support Network, London, Ontario, Canada
Indigenous Women' s Network, Lake Elmo, Minnesota; Ponsford,
Minnesota; Boulder, Colorado
Inter-Ethnic Association of the Peruvian Rain Forest (AIDESEP), Peru
International Indian Treaty Council, San Francisco, California
South and Meso American Information Center (SAIIC), Oakland,
California
l 2 3
THE GENETI CS REVDLUTI DN
Sovereignty People's Information Network, British Columbia, Canada
Tonantzin Land Institute, Albuquerque, New Mexico
Tonatierra, Phoenix, Arizona
36
On November 12-13, 1997, twenty-seven indigenous peoples' organizations
and their delegates from fifteen different nations met at an HGDP workshop in
the community of Ukupseni, Kuna Yala and issued the following declaration.
Declaration of Ukupseni, Kuna Yala
The Indigenous Peoples' organizations, gathered in the community of
Ukupseni, Kuna Yala, with regard to the Human Genome Diversity
Project (HGDP) declare:
Considering that for Indigenous Peoples, life constitutes a set of
elements forming a small universe with relationships and inseparable
harmonic dependencies, and after giving careful consideration to the
Human Genome Diversity Project and other independent investiga-
tions on the human genome, we conclude:
(a) That this research and other research projects on Indigenous Peo-
ples' genome go against human life and, in particular, violate the ge-
netic integrity of Indigenous Peoples and their values.
(b) The process of genetic collection, based on deception and exploita-
tion of poverty and marginalization, violates fundamental human
rights and collective rights, often with the consent of governments.
(c) This research is an act of piracy and theft, and consists of an assault
again Indigenous Peoples.
(d) We consider that all funding for this research constitutes an assault
against humanity and an open violation of Indigenous Peoples' rights.
(e) Having evidence that intense research already has been carried out
and continues to be done in our communities, we demand the im-
mediate suspension of these activities and the repatriation of all ge-
netic collections, original genetic material, isolated cell lines, and
the data obtained in this research.
(f) We request that the international scientific community condemn
any research that has been carried out contrary to recognized hu-
man values and moral principles, and that violates the international
codes of ethics described in the Nuremberg Code and the World
Medical Association Declaration of Helsinki.
(g) We condemn all attempts to commercialize genetic material, or ge-
netic cell lines of human beings, and in particular those of Indige-
nous Peoples.
(h) We reject the use of existing mechanisms in the legalization of
intellectual property and patent systems use of existing mecha-
nisms including intellectual property rights and patents to legalize
l 2 4
THE HGDP DEBATE
the appropriation of knowledge and genetic material, whatever their
source, and especially that which comes from our communities.
(i) For us, the concept of "individual consent" is a violation of our
cultural norms and ignores our collective rights.
(j) Indigenous Peoples do not oppose development and use of new
technologies provided they do not violate our harmonic relation-
ships, principles of solidarity, and universally recognized funda-
mental rights.
(k) We also condemn the active participation of some universities and
NGO' s who, in complicity with large transnationals, attempt to
violate the spiritual, material and political integrity of Indigenous
Peoples.
The Indigenous Peoples gathered in Ukupseni, Kuna Yala declare
that our millennial existence has been based on the principles of re-
spect, solidarity and harmony with the natural elements.
In this context, our declaration is a contribution to all of humanity.
37
On December 13, 1994, the Cordillera People's Alliance, an alliance of 120
indigenous peoples' organizations in the Cordillera region in the northern Philip-
pines, with the support of Asian and other indigenous and nonindigenous organ-
izations, issued their call for a halt to the HGDP.
Statement of the Cordillera People's Alliance
1. This is a more sophisticated form of collecting and preserving In-
digenous Peoples like those collections of yet unreturned mummies
taken from their burial caves in violation of Indigenous People's
rights.
2. The $23-35 million to be spent over five years can be better put to
providing basic social services needed for Indigenous Peoples' sur-
vival and rights protection. Fund raising for the HGDP endangers
further the chances of receiving funding for more crucial projects.
3. After the rest of the world have squandered their own resources,
the resources that Indigenous Peoples have sacrificed lives and limb
to maintain are suddenly being made common heritage for the ap-
propriation of transnationals that rarely benefit Indigenous Peoples.
Developed drugs are often sold to Indigenous Peoples at exorbitant
rates.
4. Research projects done amongst Indigenous Peoples have often
been used against them. The potential biological warfare uses are
great.
5. Indigenous Peoples used as subjects are often not fully briefed
many indigenous women have been sterilized or injected with drugs
without being informed. There is a likelihood that Indigenous Peo-
ples' poverty will be exploited to acquire test subjects.
1 2 5
THE GENETI CS REVDLUTI DN
6. The Biodiversity Convention and the Biotechnology Chapter of
Agenda 21 and the trade-related intellectual property rights of GATT
will facilitate the issuance of patents to transnational developers of
biotechnology. Many indigenous developed goods have suffered such
a fate putting them beyond the reach of IPs. The Philippine Solidarity
Group of Toronto (PSG), cognizant of these reasons, fully supports
the call to halt the Human Genome Diversity Project.
To emphasize the urgency of this call, we note two revealing
points. The HGDP draft insensitively referred to Indigenous Peoples
as "isolates of historic interest" and Luigi Luca Cavalli-Sforza wrote
in Qenomics (11:1991): "the genetic diversity of people . . . may lead
to clues of the evolution of our species. . . . " Taken together with
the trend of this project, Cavalli's phrase has the disturbing ring of
eugenicsa discredited field that seems to keep returning like the
phoenix. Further, PSG encourages other groups to show solidarity for
Indigenous Peoples struggles for aboriginal land rights and for self-
determination. It is precisely because of ethnocidethe land grabbing,
the destruction of Indigenous cultures and outright physical elimina-
tion of Indigenous communities for transnational and local big corpo-
rate and financial intereststhat Indigenous Peoples become "extinct."
In Solidarity, Philippine Solidarity Group-Toronto
38
National Research Council (NRC) Panel
In September 1996 a fifteen-person National Research Council (NRC), commis-
sioned by the National Institutes of Health and the National Science Foundation,
heard testimony from the HGDP' s organizers as well as proponents and critics.
The panel was composed of ethicists, anthropologists, geneticists, and others and
was instructed to examine issues surrounding the HGDP.
39
The NRC heard testimony that the HGDP has been awarded approximately
$500,000 in seed monies from the U.S. government and private foundations, in-
cluding the Chicago-based MacArthur Foundation. Although funding was an im-
portant consideration, a major concern was the biological significance of the
HGDP. Judith Greenberg, director of the National Institute of General Medical
Sciences division of genetics and developmental biology, questioned whether the
HGDP was the best way to get information about complex disorders or suscepti-
bility to disease.
Henry Greely and Mary-Claire King, American Society Professor at the Uni-
versity of Washington School of Medicine, as well as HGDP founder and mem-
ber of the Nort h American regional committee, responded by presenting the
document "Model Ethical Protocols for Collecting DNA Samples." The docu-
ment detailed issues such as gene patenting and informed consent.
Hope Shand, research director of RAFI, reminded the panel of past abuses of
indigenous peoples and inherent potential abuses associated with the HGDP. She
argued that many moral and ethical issues needed to be brought forth and resolved
1 2 6
THE HGDP DEBATE
before the HGDP could proceed in good faith. Other critics of the HGDP included
representatives from the Edmonds Institute (Edmonds, Washington) and RAFI,
as well as Colombia and the Solomon Islands.
Current Status of the HGDP
It is difficult to know exactly where the HGDP stands at the present time. Since
1991 when it was first proposed by Cavalli-Sforza and his colleagues, much has
happened to dampen the spirits of some of those who first proposed the project.
This author, not involved in any way with the HGDP or with any group opposing
it, finds it difficult to compare stories from one side to the other. Accurate infor-
mation is often difficult to obtain and compare since it is dispersed in so many
different sites around the world. Access to these is often not easy.
Funding remains a major problem for organizers of the HGDP. Although
there has been some limited funding, it has not been sufficient to sustain the orig-
inal purpose and goals of the HGDP. The United Nations Educational, Scientific,
and Cultural Organization (UNESCO) did not endorse the HGDP in 1995. In
1997, a report from the National Academy of Sciences recommended that the
United States National Science Foundation and National Institutes of Health not
fund the HGDP.
40
'
41
Political and public controversies have also reduced the size and scope of the
HGDP. Some of the project's strongest supporters, including Hiraku Takebe,
professor at the Atomic Energy Research Institute at Kinki University in Osaka,
Japan, appear to be somewhat pessimistic about the project. Takebe told the Hu-
man Genome Organization (HUGO) meeting in Vancouver in 2000 that he
feared the HGDP was "almost aborted" and that HUGO had not been actively
pursuing the HGDP in recent years.
42
Even with HUGO' s backing, there have been serious efforts to thwart the
project. Tactics included countries such as India forbidding the exportation of
blood samples containing DNA, and New Guinea charging a fee for each sample
taken. Other projects simulated the HGDP and drew large amounts of monies
from both private and public sources.
Some of the original backers of HGDP, including HUGO, have questioned the
organization's structure. Some view the HGDP as having ambiguous goals and ques-
tions. However, most of the organizers continue to believe keeping the (DNA) cell
lines alive for future study, as technology develops even further, to be a good idea.
"The HGDP has been a catalyst for consideration of the ethical issues that arise dur-
ing population genetics research, but itself has been plagued by the concerns to the
point where the original plan is unlikely to be completed because technical strategies
have evolved to help reduce the number of persons who need to be sampled."
43
In recent e-mail correspondence from Henry Greely at Stanford University,
he writes:
The Project never received any substantial funding. The HGDP itself
has only been able to collect samples in two of its international
regionsChina and Southwest Asiathanks to local funding in those
1 2 7
THE GENETI CS REVDLUTI DN
regions. About the only thing the HGDP is actively doing right now is
collaborating with the Center for the Study of Human Polymorphisms
(CEPH) in Paris, to make DNA available from over 1,000 cell-lines from
people around the world. Except for some of the cell-lines from China
and all of the cell-lines from Southwest Asia, these cell-lines were not
collected by the HGDP but were contributed by various researchers.
The HGDP did examine the background of the collections to assure
that each cell line had been collected with the informed consent of the
individual subjects for the use of their DNA to study broad questions
of human genetics or human history. None of the cell lines in the
HGDP-CEPH collection is from US Native Americans.
44
The HGDP has had problems carrying out its ideas and research on popula-
tions that do not share Western ideals. Because of the current political climate
worldwide, it seems poor timing to suggest what might next be possible for the
HGDP. Yet, it appears that proponents of the HGDP remain optimistic, believing
that with time and more visible work, support for the HGDP will grow.
l 2 B
PART IV
Threading an
Ethical Needle
The stem cell debate entails huge ethical principles, morality, and scientific
potential. Proponents maintain that the new technology offers great benefits for
humankind. Opponents bitterly oppose stem-cell cloning because the human
embryo is destroyed when stem cells are removed. In arriving at a consensus on
the value of stem-cell research we must look to the past, examine the current re-
search, and project the merits of the technology for the good of society.
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s
STEM- CELL RESEARCH
Our intention is not to create a cloned human being, but rather
to make life-saving therapies for a wide range of human disease
conditions, including diabetes, strokes, cancer, AIDS, and neu-
rodegenerative disorders such as Parkinson's, Alzheimer's, and
multiple sclerosis.
Robert Lanza, Director of Medical Research,
Advanced Cell Technology
Stem-cell research took a giant leap in April 2001 when Dr. Judson Somerville, a
forty-year-old Texas physician paralyzed from the chest down as a result of a cy-
cling accident, took a cigar-cutter and cut a chunk of skin from his right calf for a
cloning experiment. The goal was to grow a new organ such as a heart for a heart
patient, some brain tissue for an Alzheimer's patient, or some diabetic cells for a
diabetic patient from the skin cells, or perhaps even providing some neurons
(nerve cells) that would cure his own paralysis.
1
Although Somerville does not believe in cloning humans, he has a firm belief
in stem-cell research. "I don' t want another one of me. I want my own neurons so
I can walk again or feel below my chest."
2
Offering Hope
Stem cells, obtained from human embryos, are useful in repairing and replacing
damaged cells such as Somerville's neurons and offer the promise of curing many
individuals with various diseases, including but not limited to cancer, Alzheimer's,
THE GENETI CS REVDLUTI DN
Parkinson's, multiple sclerosis, chronic heart disease, rheumatoid arthritis, os-
teoarthritis, liver failure, diabetes, amyotrophic lateral sclerosis, muscular dystro-
phy, and spinal-cord injuries.
Other examples of potential cures, using embryonic stem cells, include skin
damaged by burns and bone mass depleted by osteoporosis. In addition, gene-
tically engineered stem-cell cultures potentially may be used for both transplants
and evaluating drugs in labs. This often overlooked, but profoundly important,
procedure has the potential to rule out dangerous drugs before they are tested on
humans.
Embryonic stem-cell cloning is of great interest to scientists and physicians
who believe they have a moral obligation to improve the lives of future genera-
tions. Yet, as with any scientific or technological advancement, the most impor-
tant question that needs to be asked is whether or not the gains outweigh the
potential losses.
Stem-cell cloning allows a patient' s own DNA to be used to develop ad-
vanced medicine and offers hope to the nearly 100 million Americans who suffer
from diseases and the thousands who die each day as a result of incurable dis-
eases. Unfortunately, while the huge controversy continues over cloning using
embryonic stem cells, thousands of individuals die each each day as scientists and
policy makers continue to study the issue and attempt to make decisions. "Three
thousand Americans die every day of diseases that therapeutic cloning could
treat. It would be wrong of us to abandon those people because we're afraid of
controversy."
3
Whereas opponents of embryonic stem cell research have a great deal of em-
pathy for those who suffer with various diseases, at the same time they bitterly
oppose stem-cell cloning because the human embryo is destroyed when stem cells
are removed. Stem-cell cloning is a technique used by researchers and animal
breeders to split a single embryo into two or more embryos. The most unique
feature of embryo cloning is that scientists can grow undifferentiated stem cells
and transform them into more than 200 of the body' s specialized cell types that
humans need for development. In 1998 scientists discovered how to isolate and
grow embryonic stem cells so that the cells maintained their pluripotencythey
remain a seemingly endless source of any kind of cell.
Recently, Dr. John D. Gearhart and his team at Johns Hopkins University
figured out how to t urn human embryonic stem cells into an infinite number of
different kinds of cells, including heart muscle, skin cells, and T cells of the
immune system. However, even though embryonic stem cells are able to differ-
entiate into other cell types, they are not able to differentiate into a complete in-
dividual.
All human embryos in their earliest stages of development contain stem cells
that have a capacity to replace almost any damaged or defective tissue in the
body. By cloning human embryos for the production of stem cells that perfectly
match a patient' s cells, transplant organs can be grown that provide a perfect ge-
netic match. Importantly, embryonic stem cells are unspecialized (undifferenti-
ated) and are not attacked by the person' s own immune system.
There is potential for millions of people worldwide to reap the benefits of
embryonic stem-cell research. Among those who will benefit are children with
1 3 2
STEM- CELL RESEA RCH
Type I, juvenile insulin-dependent diabetes who could be supplied with the pan-
creatic islet, insulin-producing cells they now lack. In August 2001 a team in
Israel, using human embryonic stem cells developed by scientists at the Univer-
sity of Wisconsin, reported they had programmed embryonic stem cells to pro-
duce insulin.
4
Another prime example of how stem cells offer great hope is regeneration of
neurons in treatment of diseases such as amyotrophic lateral sclerosis (Lou
Gehrig's disease), multiple sclerosis, and spinal-cord injuries. Gearhart and col-
leagues at Johns Hopkins University programmed embryonic stem cells to begin
functioning like neurons. Gearhart injected programmed stem cells into the cere-
brospinal fluid which surrounded injured spinal cords of rats. Three months
later, many of the once paralyzed rats were able to walk again. In another signifi-
cant study, Harvard scientists used embryonic stem cells in mice that had a
multiple-sclerosis-type disease. Scientists used the stem cells to repair myelin, the
fatty material that covers central nervous system neuronal axons.
5
Stem-cell-derived neurons also have the potential to treat Alzheimer's and
Parkinson' s diseases and to repair spinal-cord injuries. Using stem cells, scientists
have done a great deal of work in providing Parkinson' s patients with new brain
cells. In Parkinson' s disease people lose brain cells that produce dopamine, a
chemical (neurotransmitter) responsible for controlling nerve signals that regu-
late movement. In treating Parkinson' s patients, surgeons drill through the skull
and implant reprogrammed stem-cell-derived neurons. Transplanting dopamine-
producing neurons alleviates the tremors and impaired balance that are among
the major symptoms of Parkinson's.
Another example of embryonic stem cell use is in stem-cell-derived heart mus-
cle cells (cardiomyocytes) that have the potential to repair or replace a damaged
heart. Heart patients could receive programmed cardiac cells that would enable sci-
entists to grow new cardiac tissue rather than having to rely on a mechanical heart
or a heart transplant.
In early September 2002 it was announced in Amsterdam, the Netherlands,
that a three-year-old blond, blue-eyed boy named Wilco Conradi had been
treated with embryonic stem cells. Wilco had been born with severe combined
immunodeficiency (SCID), a disease that occurs in about one of every 15,000
births. SCID, which is carried by women but afflicts only boys, had plagued
Wilco' s family for generations, killing one of his uncles and two cousins.
SCID makes the immune system ineffective against microorganisms ordinar-
ily harmless in people with normal resistance. In order to give Wilco a normal im-
mune system, he was injected with genetically modified embryonic stem cells.
Wilco had been treated as a baby at the Hospital Necker Enfants Malades in Paris
and had lived his first months in a germ-proof plastic enclosure to protect him
from infections that would have been fatal to him. Previously, bone-marrow
transplants had been the method of choice to help victims of SCID, followed by
monthly intravenous infusions of immune globulin antibodies taken from do-
nated blood.
The potential for embryonic stem-cell research is not limited to those who
suffer from life-threatening diseases. Stem-cell research also presents a realistic
potential to curing some of the diseases that accompany aging. Gerontologists
1 3 3
THE GENETI CS REVDLUTI DN
are especially optimistic about the prospects of using embryonic stem cells to re-
place cartilage destroyed by arthritis in the elderly.
In early times, researchers never even came close to knowing the secret of ag-
ing and some of its manifestations: "English scientists of the 13th century there-
fore believed that the breath of a virgin would rejuvenate old men, while a
physiologist in 1920's Vienna theorized that elderly men would find renewed
vigor and extra years by having the testicles of younger men grafted onto their
original equipment. Neither approach, needless to say, worked. But today' s re-
searchers are thinking along the same lines. To replace and repair cells damaged by
the diseases of aging, go to the youngest of the young: days old human embryos."
6
Other Recent Breakthroughs
Recently, in a significant breakthrough, it was reported that embryonic stem cells
can be coaxed to transform themselves into eggs for stem-cell cloning. Researchers
at the University of Pennsylvania reported they were able to cause stem cells
from mouse embryos to transform into oocytes (eggs) and to further develop into
primitive embryos. The embryos cannot be used to reproduce mice because they
contain an incomplete set of chromosomes; however, the eggs can be used for
embryo cloning. The study, conducted by Hans Scholer and colleagues of the
School of Veterinary Medicine at the University of Pennsylvania, suggests that
eggs can be made in the laboratory from stem cells. This is highly significant be-
cause it would eliminate the need for embryo donors and lead to an almost limit-
less supply.
7
Although embryos are the choice for obtaining stem cells, adult stem cells
are found in many tissues, including blood, liver, brain, nerve tissues, adult fat,
umbilical cords, and placentas. In addition, multipotent adult progenitor cells
(MAPCs), also known as "master cells," have been found in the bone marrow.
MAPCs have the potential to be a major source of stem cells. The chief disad-
vantage of adult stem cells is that they do not have the same versatility as embry-
onic stem cells to differentiate into specific cell or tissue types. Another
disadvantage is that adult stem cells can double only a few times in culture, allow-
ing replication of only a few stem cells. Millions, or perhaps billions, of stem cells
are needed for major organ repair, made possible by culturing embryonic stem
cells. Efforts are currently underway to try to coax adult stem cells back to an em-
bryonic state.
Recently, at the Stem Cell Institute at the University of Minnesota,
Dr. Catherine Verfaillie and her team reported that certain bone-marrow cells
taken from adult humans give rise to a variety of other cell types in the test tube.
The study, done in test tubes and mice, suggests that adult stem cells might be an
alternative to embryonic stem cells, at least in some cases.
A new discovery in 2004 is using stem cells to grow new adult teeth to replace
lost or diseased ones. Scientists at the National Institute of Dental and Craniofa-
cial Research have used human adult stem cells from extracted molars to grow
new tooth buds that are implanted into animals' jaws and develop into new teeth.
Another research team, directed by Paul Sharpe of King's College in London,
1 3 4
STEM- CELL RESEA RCH
grew new teeth in mice from nondental mouse stem cells. The team began exper-
iments in 2005 with human cells.
Another recent development in stem cells was effected by scientists at the
University of Toronto and Miami University in Ohio, who transplanted stem
cells from a human retina into the eyes of day-old mice and chick embryos. When
the animals' eyes developed fully, the scientists found that many of the human
cells had survived and grown into specialized cells needed for sight. The re-
searchers examined the eyes, which appeared to be normal. It is now thought that
the retinal stem cells from healthy mice will continue to develop when trans-
planted into blind mice. The research is a key advance in the use of stem cells to
treat disorders such as macular degeneration and retinitis pigmentosa.
In yet another noteworthy development, surgeons at the Justus-Liebig Univer-
sity Medical School in Giessen, Germany, used stem cells from a seven-year-old
girl's fat to help repair severe damage to her skull. This was the first time that re-
searchers have generated bone in a person by using the fat-derived cells. This is an
example of the use of adult stem cells rather than embryonic stem cells to treat dis-
ease. The girl, a victim of a severe fall two years prior to the treatment, was missing
nineteen square inches of her skull. After the stem-cell surgery, the girl's skull was
reported smooth to the touch, the missing parts replaced by thin but solid bone.
In May 2005 it was announced that South Korean scientists were speeding up
the process of creating human embryonic stem cells, growing new batches that
were, for the first time, a genetic match for injured or sick patients. Patients were
male and female, as young as age two and as old as fifty-six, suffering with spinal
cord injuries, diabetes, or genetic immune diseases. The Seoul researchers, led by
Woo-Suk Hwang and Shin Yong Moon of Seoul National University, eliminated
the use of mouse "feeder cells" that were used to nourish human stem cell lines,
causing concerns about animal contamination.
The researchers collected eggs that were donated by unpaid volunteers and
removed the gene-containing nucleus from each egg. The scientists inserted into
the eggs DNA from skin cells of the patients and electrically stimulated cellular
division. Thirty-one early stage embryos (blastocysts) of 100 cells each success-
fully grew. From those, the scientists harvested eleven stem cell lines. Each line
was a genetic match to the patient who donated the skin snippet, and each has the
potential to form other tissues, such as brain cells or bone cells. The use of skin
cells is not only easier but extends the technology to both males and females.
The procedure, called nuclear transfer or therapeutic cloning, is permitted in the
United States under Proposition 71, passed in November 2004 in California.
The advance does not, however, change the fact that the human embryo must be
destroyed to obtain stem cells. Leon Kass, M.D., chairman of the President's
Council on Bioethics and professor metaphysics and moral philosophy at
Georgetown University, described the Korean research as "morally troubling."
Unlike the United States, the South Korean government supports financing
stem cell research. The same is true in Singapore where $1.5 billion is given by the
government to its renowned Biopolis research center. The Biopolis has many
cutting-edge laboratories and has recruited top researchers from around the
world. In August 2004, Britain granted its first license to Newcastle University
for human cloning, joining South Korea on the leading edge of stem-cell research.
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THE GENETI CS REVDLUTI DN
Obtaining Stem Cells
Different procedures are used to obtain stem cells. When therapeutic cloning
(also known as somatic cell nuclear transfer technology) is used, scientists remove
the nucleus of an egg cell and replace it with materials from the nucleus of a so-
matic (body) cell such as Dr. Somerville's skin, a nerve, heart, or any other non-
germ cell. Scientists then stimulate the cell by electrical or chemical means to
begin cell division. The resulting cells are never transplanted into a womb for
subsequent development into a human being, but rather are kept in a petri dish in
the laboratory where they are eventually used to obtain embryonic stem cells.
For a few days, each embryonic stem cell is a "blank page," awaiting a com-
plex set of genetic instructions to determine precisely which organs, bone, and
specialized tissues and cells to form. What the stem cells actually become de-
pends on which of the 30,000 or so genes (individual in every human cell) are
turned on. For example, if genes characteristic of pancreatic cells t urn on, while
genes characteristic of all other cells remain turned off, the stem cells grow into
pancreatic cells. If genes characteristic of dopamine-producing neurons t urn on
while other genes are turned off, the specific stem cells grow into dopamine-
producing cells.
Sexual fertilization is used for stem-cell production. After a sperm fertilizes
an egg the embryo is allowed to develop and the stem cells are removed from the
four-to-six-day-old embryo. Removing the stem cells kills the blastocyst (pre-
embryo), a hollow ball of 200 cells. After removal from the blastocyst, stem cells
are nurtured in a medium of proteins and enzymes where they divide indefinitely,
creating a lineage of specialized cells called an embryonic stem-cell line.
So far, scientists have revealed three established sources of human embryos
needed for stem-cell cloning. Each of these methods crosses different moral, eth-
ical, and legal lines.
Excess (surplus) frozen embryos currently are obtained mostly from in
vitro fertility clinics and are donated by infertile couples who no
longer want them for pregnancy. Frozen embryos are the most widely
accepted source of embryos. Destined to be destroyed, the few-days-
old frozen embryos are thawed and the inner cell mass containing the
stem cells is removed. Various groups on the Christian Right and the
Roman Catholic Church regard frozen in vitro fertilized embryos as
human beings.
Fresh embryos (contrived conception) are created specifically for research
by fertility clinics that gain consent from donors to fuse an egg and a
sperm for the intentional purpose of creating an embryo, specifically
for harvesting stem cells.
Cloned (coupled and copied) embryos are created by combining donor
eggs and cells using experimental cloning techniques. Using an electri-
cal current, cells from a donor (preferably the person to receive the
stem cells) are fused with an egg stripped of its nucleus. Reprogrammed
with the donor' s genetic material, the egg is tricked into developing
l 3 6
STEM- CELL RESEA RCH
and yielding stem cells. The stem cells are harvested and reprogrammed
into dividing and forming colonies identical to the parent cells.
Antiabortion activists and various religious groups consider all three tech-
niques unethical, saying they result in the destruction of human life. However,
proponents of stem cell research argue that these days-old, undifferentiated cells
cannot be viewed as human since they will never be implanted in a woman with
the intent to produce babies.
In a newer technique, called pre-implantation analysis, actual cases like the fol-
lowing hypothetical one may soon become commonplace:
Maya and Dick Anderson of Lakewood, California, went through in
vitro fertilization and genetic testing of son David' s embryo to make
sure he did not have the gene for the always-fatal disease, Fanconi's
anemia, that his sister, Susie, had. The Andersons also wanted to make
sure David could provide transplant cells for Susie after he was born.
Geneticists examined fifteen embryos that had been created using
eggs and sperm from the Andersons and determined that David' s em-
bryo did not carry the Fanconi's anemia gene. Thus, they implanted
David' s embryo in Maya Anderson' s uterus and allowed David to de-
velop into a full-term baby. The remaining embryos were frozen.
David was born in August 2003 and stem cells were taken from his
umbilical cord blood and implanted into his sister Susie. Physicians at
Duke University, where the transplant took place, said results were
successful.
Leftover Embryos
Frequently, there is little interest on the part of couples who create embryos as
what to do with their embryos that they no longer need or want. Unable to face
the difficult decision for one reason or another, many couples leave their em-
bryos frozen, often paying hundreds of dollars each year in storage fees, some as
high as $1,000 or more per month. It is estimated that there are over one million
early embryos (blastocysts) leftover worldwide from in vitro fertilization, waiting
to be discarded. The following hypothetical case is an example:
In vitro fertilization brought Lori and Joe Haley two sons and a daugh-
ter but left them with a dilemma: what to do with three extra embryos
left frozen in a Los Angeles clinic. It often takes several tries to get an
embryo to attach to the uterus and grow into a fetus, so fertility spe-
cialists routinely collect and fertilize as many eggs as possible and then
choose the healthiest. As a result, leftover embryos are frozen to try
again later or in cases like the Haleys who have all the children they
want, the frozen embryos remain. The Haleys did not want to throw
their embryos away now that they had no further need for them. In ad-
dition to disposal of the embryos, their options included donating
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THE GENETI CS REVDLUTI DN
them to research or giving them to another couple who were trying to
have a baby.
Some embryo donors cannot abide with the prospect of their genetic chil-
dren being raised by someone else, whereas others worry that one of their chil-
dren might unknowingly meet and fall in love with a brother or sister. Others
have long-term guilt in throwing away their embryos; some have guilt for the rest
of their lives. For many couples, donating unwanted embryos for stem-cell re-
search appears to be a more comfortable option than donating them to a couple
for family building.
Stem Cell Debate
The stem cell debate is about huge ethical principles, morality, and scientific
potential. The debate over embryonic stem-cell use intensified with word that sci-
entists at Advanced Cell Technology Inc. (ACT) in Worcester, Massachusetts, had
cloned for the first time a six-cell human embryo for its stem cells. Officials at
ACT repeatedly emphasized that the cloned human embryo was created to pro-
vide genetically compatible matched cells for patients suffering from a wide range
of diseases, rather than to create a cloned human being: "Our intention is not to
create cloned human beings, but rather to make life-saving therapies for a wide
range of human disease conditions, including diabetes, strokes, cancer, AIDS, and
neurodegenerative disorders such as Parkinson' s and Alzheimers disease."
8
In general, opponents of stem-cell research believe that destroying an em-
bryo, even for curing diseases, is morally repugnant, unethical, and medically un-
necessary and view it as an evil act that can never be justified. The Roman
Catholic Church has led opposition to human embryonic stem-cell research be-
cause of what it calls the "sanctity of life." Catholic doctrine holds that life be-
gins at conception, which means that an embryo, even at its very earliest stage of
development, is regarded as human life. Others fear that creating embryos for
their stem cells will get out of control or in the hands of evil persons. Still others
argue that embryonic stem-cell research must not be established in law because
people, no matter their size or stage of life, are not products to be used for the
benefits of others, no matter how noble the intentions.
Some believe that if the Hippocratic Oath taken by physicians is abandoned,
it will signify that the end justifies the meansthat it is permissible to kill some
people so long as physicians intend to do good for others. Yet, most physicians
and scientists who are proponents of stem-cell cloning agree that it offers treat-
ment and cures for many diseases and that they owe it to posterity to pursue it.
With the potential to ease a great deal of pain and suffering, physicians and sci-
entists also believe that stem-cell cloning would help not only those individuals
who suffer from terrible ailments, but would also include victims' families and
friends.
Dr. Bert Vogelstein of the Johns Hopkins University School of Medicine,
who chaired a National Academy of Sciences Report that endorsed stem-cell re-
search, wrote: "The scientific obstacles surrounding stem-cell research are just as
l 3 8
STEM- CELL RESEA RCH
real as the ethical or legal concerns. If the nation wants to reap the benefits of
stem-cell research, then these barriers must be overcome."
9
The prevailing view among scientists is that it is acceptable to destroy em-
bryos for medical research as long as the embryos are destined to be destroyed
anyway. The National Institutes of Health established guidelines during the Clin-
ton administration that permitted federal funding of research on surplus frozen
embryos from fertility clinics. This required the consent of couples who had the
embryos created for the purpose of having a baby.
The American Society of Reproductive Medicine, representing the nation' s
fertility doctors, issued a statement saying that it was ethical to create embryos
for research. The argument set forth by fertility doctors was that it was a more
"ethically pure" way to conduct the research than to ask couples to donate em-
bryos. The U.S. government supported the work of medical researchers who
were using human stem cells obtained from sources that did not require the de-
struction of human embryos. Current NIH guidelines ban funding of embryos
that are created specifically for research.
Part of the hysteria of embryo cloning is a misunderstanding of what an em-
bryo actually is. Michael West, visionary for ACT, said: "If you ask the average
person, they will tell you it's a tiny little person with buggy eyes. But in fact, these
are just a few reproductive cells, not much different than eggs or sperm. They are
the raw materials of life, but they are not a person."
10
However, David Oderberg, a professor of philosophy at the University of
Reading in the United Kingdom, has a different view: "An embryo is a human
being and may not be destroyed for any purpose, any more than a baby or an
adult can be. Every innocent human being, no matter how big, small, healthy or
sick they are, has an inalienable right to life."
11
Oderberg' s statement begs the question, is there an inalienable right to life? If
so, why are embryos an exception? But ethicists argue the fact that embryos cre-
ated in vitro (in a petri dish) and in vivo (in the body) are different, a term called
nonenablement.
Another serious obstacle standing in the way of successful medical treatment
with human embryonic stem cells is immune system rejection. Both frozen and
fresh stem cell lines are from donors unrelated to the patient who would receive
the cells as transplants. Patients would be required to take antirejection drugs,
which could have serious side effects. To circumvent rejection, scientists have to
make the cells acceptable to a recipient's immune system.
There is also controversy over whether taxpayer monies should be used to
fund research that many people consider morally wrong. Although U.S. Federal
law currently prohibits the use of taxpayers' money for the cloning of human be-
ings, privately funded companies such as ACT are not affected by the ban.
Leading the Way
Many companies are currently involved in stem-cell research. Leading the way
with transfer of human DNA into human eggs and the growth of the eggs into
six-cell embryos was Advanced Cell Technology (ACT), a small biotech company
1 3 9
THE GENETI CS REVDLUTI DN
in Worcester, Massachusetts Founded in 1994, ACT since has offered a wide ar-
ray of genetic services, including in vitro fertilization and cloning for cattle.
The first of three men at ACT to be credited with pioneering embryo cloning
was Jose Cibelli. Considered the "instigator," Cibelli, a native of Argentina and a
doctoral student working in the laboratory of James M. Robl at the University of
Massachusetts-Amherst, was instrumental in stem-cell cloning. Robl, a profes-
sor of veterinary and animal science, had previously cloned cattle, pigs, and rab-
bits. After joining ACT, Cibelli described what he perceived as the "future of
medicine"human stem-cell cloning.
12
The second man involved with stem-cell cloning at ACT, geneticist Michael
West, was considered the "visionary." ACT' s focus shifted to humans in 1998
when West took over the company. A "creationist," West had a passion for alle-
viating suffering, using stem-cell cloning: "If God is about love and life, then we
should do everything we can to end suffering and death."
13
West had reincorporated his late father's truck-leasing business as a biotech
firm called Geron (Greek for "old man"), with a primary goal to reverse aging and
some of its main afflictions: macular degeneration, cancer, Alzheimer's, and heart
disease. West' s wife, a prominent scientist in her own right, had previously cloned
the gene for telomerase, the enzyme that extends the life of telomeres, structures in
the cell that decide whether a cell is to age and/or die.
14
West joined forces with Cibelli, who had demonstrated an alternate way to
engineer an embryo by coaxing a human egg to divide and develop into an em-
bryo without any kind of fertilizationeither by a sperm or outside genetic ma-
terial (DNA)a process known as parthenogenesis (Greek for "virgin birth").
Cibelli tricked the eggs into keeping copies of their chromosomes for develop-
ment. Human parthenogenesis had never been reported before; however, certain
lizards, microbes, insects, and other animals naturally reproduce through partheno-
genesis.
Cibelli and his colleagues believed that stem cells had the potential of being
retrieved from a parthenogenetic embryo in women of childbearing age because
they could produce a sufficient number of eggs. The scientists speculated that it
would be possible to replace the egg's DNA with genes from sperm and the egg
then could be activated to become a parthenote.
15
The third man at ACT, Robert Lanza, was considered the "activist." As a
young scientist he was mentored by some of the scientific giantspsychologist
B. F. Skinner, immunologist Jonas Salk, and heart transplant pioneer Christian
Barnard. Highly regarded by his peers and mentors, Lanza became director of
medical research at ACT in March 1999. Lanza had strong beliefs that cloning
could end transplant rejection, and persuaded sixty-seven Nobel laureates to sign
a letter that was sent to President Clinton in support of embryonic stem-cell re-
search.
However, over a two-year period (1999-2001), West, Cibelli, and Lanza lost
some respect throughout the scientific community. Called "mad scientists,"
"baby killers," and "monsters," among other names, they were put on antiabor-
tion assassination lists on the Web and warned by the FBI of threats on their
lives. A bill presented to the House of Representatives declared them federal
criminals deserving of ten years in prison and a $1 million fine.
16
Some of their
1 4-D
STEM- CELL RESEA RCH
troubles came as a result of ACT' s work with human embryos, since embryos
could be implanted into a womb and grown into a fetus. However, the ACT sci-
entists preferred the term
u
ovum sum,
11
to embryo.
Potential to Heal
Today, most U.S. stem-cell research is done in private labs and biotech companies
that are not affected by federal guidelines. Each company employs different, but
sometimes controversial, techniques to harvest embryonic stem cells. Various
well-known universities are working to create stem cell lines with funds from pri-
vate organizations such as the Juvenile Diabetes Research Foundation, the
Christopher Reeve Paralysis Foundation, the Michael J. Fox Foundation for
Parkinson' s Research, and Stanford University's Institute for Cancer/Stem Cell
Biology and Medicine. Christopher Reeve (who died in 2004) suffered a spinal
cord injury and Michael J. Fox is a Parkinson' s victim.
In 1998 James Thompson pioneered research on human embryonic stem
cells at the University of Wisconsin-Madison. Thompson created five colonies
of stem cell lines from human embryos. WiCell Research Institute, a nonprofit
company formed in 1999 by the Wisconsin Alumni Research Foundation (WARF),
also further advanced research in the area of stem cells. Founded in 1925, WARF
patents research discoveries at the University of Wisconsin-Madison and man-
ages patents and technology transfers to industry.
Because federal law prohibits public funding of human embryo experiments,
Thompson used private funding from Geron Corporation, located at Menlo
Park, California, to buy leftover frozen embryos from fertility clinics. Since that
time, Geron has announced plans to obtain its stem cells by cloning proteins in
eggs that would lead to the creation of stem cells.
Michael West, president of ACT, announced that his company intended to
clone human embryos as sources of stem cells using a new technique that would
provide an alternative to creating embryos as sources of stem cells. He an-
nounced that a patent was pending on the technique, called ooplasmic transfer,
which would allow scientists to create stem cells directly without first making an
embryo.
Working with university labs, ACT has shown some very promising stem-cell
research. In animals, body cells have been taken and cloned to generate embryos.
Stem cells have been extracted from the embryos to grow new tissues and some
diseases have been cured. For example, in sheep, replacement neurons have cured
spina bifida. Old cows have been given new "young" immune system cells. Tiny
kidneys, grown from cloned cells, reportedly have functioned properly for three
months in cows. Embryonic stem cells have been injected directly into sheep and
become disks of bone and perhaps the replacement for liver and brain cells.
Patches of heart muscle, skeletal muscle, skin, and cartilage have been grown
from cloned embryos and transferred back into the parent cows. ACT hopes to
be able to change DNA, removed from a body cell, before it is placed into an egg,
by adding factorsgenes for immune cells that would make a person resistant to
diseases.
17
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THE GENETI CS REVDLUTI DN
Other private companies have established collaborative arrangements with
Universities. Boston in Vitro Fertilization, the country' s largest infertility clinic,
has provided embryos to Harvard University scientists, who extract stem cells
from the embryos. Boston IVF contacts thousands of couples with long-frozen
embryos to ask whether they want to donate their embryos for stem-cell re-
search. The project has been financed by the Howard Hughes Medical Institute.
Using donated sperm and eggs, human embryos have been created by the
Jones Institute for Reproductive Medicine, located in Norfolk, Virginia. The in-
stitute fertilizes them with the same techniques used for generating embryos for
infertile couples. Created solely for research purposes, the embryonic stem cells
were available under President Bush's guidelines because the embryonic cells are
created with informed consent of donors from excess embryos originally in-
tended for human reproduction.
In early December 2002 Stanford University became the first U.S. university
to publicly announce that it had plans to develop stem-cell research through a
highly experimental scientific method. The research is taking place at Stanford's
new Institute for Cancer/Stem Cell Biology and Medicine and is led by Irving
Weissman, a leader in stem-cell research.
18
Stanford's new institute is privately
funded to avoid any conflict with President George W. Bush's policy against us-
ing federal funds to create new stem-cell lines. The institute and its scientists are
reportedly opposed to human reproductive cloning.
Other scientists are involved in an emerging field of medicine that involves
control of blood vessel growth by stem cells. In August 2002 an article published
in the medical journal Lancet was the first to report that patients' own stem cells
were injected into their leg muscles to create new blood vessels (therapeutic angio-
genesis), eliminating pain from bad circulation and helping to prevent gangrene or
amputations. The main focus of such research is on the heart, limbs, and brain.
Another major use of angiogenesis are sores that fail to heal, in the case of di-
abetes. Findings such as these offer hope to millions of people worldwide who suf-
fer pain in their limbs because of clogged arteries but cannot have an operation.
19
The Political Side
On September 22, 2001, Governor Gray Davis of California, believing stem-cell
research was essential to keep California at the forefront of medical research,
signed a bill authored by Senator Deborah Ortiz to allow embryonic stem cell re-
search in California. Governor Davis was joined at the ceremony by actor
Christopher Reeve, who was paralyzed in a horse riding accident in 1995.
The bill allowed for both the destruction and donation of embryos. In addi-
tion, the bill required clinics that perform in vitro fertilization procedures to in-
form women that they have the option to donate discarded embryos to research;
the bill banned the sale of embryos. Ortiz' s bill was openly opposed by the Ro-
man Catholic Church and antiabortion groups because the embryo is destroyed
in the process.
Because obtaining embryonic stem cells for research destroys human em-
bryos, the practice is viewed by many as immoral. Although stem cell research
1 4 2
STEM- CELL RESEA RCH
came at an ethical cost for society, it came as a political cost for President George
W Bush from his most conservative political and religious supporters. The pres-
ident' s decision on embryonic stem-cell research represented the most socially
acceptable means of sacrificing embryos for research. In making his decision,
President Bush balanced the issues. The president reassured conservatives that
he would never permit federal funding of stem-cell research that required the de-
struction of human embryos. The president promised to allow funding for re-
search on only a limited number of existing stem-cell "lines."
How Far? How Fast?
How far, and how fast, stem-cell research progresses will depend mostly on the
outcome of the heated political battle that continues over the use of human em-
bryos as a source of stem cells. Realistically, it will probably be many years before
the research yields a viable product. A good example of how slowly science pro-
ceeds is that scientists started working with genetic engineering in the early 1970s
and it took more than a decade before recombinant DNA products hit the mar-
ket. It took in vitro fertilization even longer before it was accepted into society.
Although currently banned in the United States, human embryo research
continues overseas. In February 2004 South Korean scientists cloned an embryo
and extracted the stem cells from it. In another case, Professor Song Chang-hun
of Chosun University treated a thirty-seven-year-old spinal-cord patient with
umbilical cord stem cells. The patient had been in a wheelchair for nineteen years,
and forty days after treatment stood up and walked with the help of a walker. Re-
searchers hope eventually to create insulin-producing cells that could be trans-
planted into diabetics.
Regardless of the political dispute and its outcome, stem-cell research will go
forward in the United States with private, if not public, financing. Scientists owe
it to posterity to pursue stem-cell research, proceeding with great care, vigilance,
and restraint. The technology has enormous potential and benefits for those suf-
fering from many devastating diseases.
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9
A MAJDR DECI SI ON
At its core, this issue [stem cell research] forces us to confront
fundamental questions about the beginnings of life and the ends
of science.
President George W. Bush
In a long-awaited decision that resulted in a passionate political and ethical de-
bate, President George W. Bush, in an August 9, 2001, prime-time speech to the
nation, gave the go-ahead for limited federal funding on existing human embry-
onic stem cells. In the eleven-minute speech, the president was deliberate and well
grounded and came across as thoughtful and serious:
Good evening. I appreciate you giving me a few minutes of your
time tonight so I can discuss with you a complex and difficult issue, an
issue that is one of the most profound of our time. . . .
My administration must decide whether to allow federal funds,
your tax dollars, to be used for scientific research on stem cells derived
from human embryos. A large number of these embryos already exist.
They are the product of a process called in vitro fertilization, which
helps so many couples conceive children. When doctors match sperm
and egg to create life outside the womb, they usually produce more
embryos than are implanted in the mother. Once a couple successfully
has children, or if they are unsuccessful, the additional embryos re-
main frozen in laboratories.
Some will not survive during long storage; others are destroyed. A
number have been donated to science and used to create privately
THE GENETI CS REVDLUTI DN
funded stem-cell lines. A few have been implanted in an adoptive
mother and born, and are today healthy children. . . .
You should also know that stem cells can be derived from sources
other than embryosfrom adult cells, from umbilical cords that are
discarded after babies are born, from human placentas. And many sci-
entists feel research on these types of stem cells is also promising.
Many patients suffering from a range of diseases are already being
helped with treatments developed from adult stem cells.
However, most scientists, at least today, believe that research on
embryonic stem cells offers the most promise because these cells have
the potential to develop into all of the tissues in the body. . . .
Research on embryonic stem cells raises profound ethical ques-
tions, because extracting the stem cell destroys the embryo, and
thus destroys its potential for life. Like a snowflake, each of these
embryos is unique, with the unique genetic potential of an individual
human being.
As I thought through this issue, I kept returning to two fundamen-
tal questions: First, are these frozen embryos human life and therefore
something precious to be protected? And second, if they' re going to
be destroyed anyway, shouldn' t they be used for a greater good, for re-
search that has the potential to save and improve other lives? . . .
At its core, this issue forces us to confront fundamental questions
about the beginnings of life and the ends of science. . . .
Researchers are telling us the next step could be to clone human
beings to create individual designer stem cells, essentially to grow an-
other you, to be available in case you need another heart or lung or
liver.
I strongly oppose human cloning, as do most Americans. We re-
coil at the idea of growing human beings for spare body parts, or cre-
ating life for our convenience. . . .
I have friends whose children suffer from juvenile diabetes.
Nancy Reagan has written me about President Reagan's struggle with
Alzheimer's. My own family has confronted the tragedy of childhood
leukemia. And, like all Americans, I have great hope for cures.
I also believe human life is a sacred gift from our Creator. I worry
about a culture that devalues life, and believe as your president I have an
important obligation to foster and encourage respect for life in America
and throughout the world. . . .
Embryonic stem cell research offers both great promise and great
peril. So I have decided we must proceed with great care.
As a result of private research, more than 60 genetically diverse
stem cell lines already exist. They were created from embryos that
have already been destroyed, and they have the ability to regenerate
themselves indefinitely, creating ongoing opportunities for research. I
have concluded that we should allow federal funds to be used for re-
search on these existing stem cell lines, where the life and death deci-
sion has already been made. . . .
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A MA JDR DECI SI ON
I also believe that great scientific progress can be made through
aggressive federal funding of research on umbilical cord, placenta,
adult and animal stem cells, which do not involve the same moral
dilemma. . . .
I will also name a President's council to monitor stem cell re-
search, to recommend appropriate guidelines and regulations, and to
consider all of the medical and ethical ramifications of biomedical in-
novation. . . .
As we go forward, I hope we will always be guided by both intel-
lect and heart, by both our capabilities and our conscience.
1
The President's Main Concern
In arriving at his decision, the president had a moral and ethical concern because
he believes life begins at conception. From the beginning, he made it clear that he
believed the risks and ethical issues associated with human cloning outweighed
any potential benefits to science. Addressing a Whi t e House audience filled with
supporters of a ban on cloning, the president stated: "Our children are gifts to be
loved and protected, not products to be designed or manufactured. No human
life should be exploited or extinguished for the benefit of another."
2
The president' s decision was not a total restraint, but rather a compromise.
Accepting stem-cell lines in existence as of his August 9 speech, the president
said he would not allow taxpayer money to go toward creating more stem-cell
lines because it would involve destruction of more human embryos. Attempting
to thread an ethical needle, the president' s compromise allowed him to address
concerns about the willful destruction of potential human life, while at the same
time gave hope to those suffering with destructive diseases that might potentially
be cured by embryonic stem-cell research.
In forming his resolution, the president decided that a few stipulations must
be followed. First, human embryos must have been created for in vitro fertiliza-
tion (IVF) and no longer wanted for that purpose. Couples with leftover embryos
could still donate them for research, but only if privately funded. Private groups
operating without federal funds could still create and clone embryos. Second, in-
formed consent must have been obtained for the donated human embryo cells.
President Bush announced that he would offer half of the federal money for
research on human embryonic stem cells to the University of Wisconsin Alumni
Research Foundation, a biotechnology company known as the WiCell Research
Institute, and Geron Corporation of Menlo Park, California, to pay royalties and
licensing fees on patents.
Not an Easy Decision
It was not an easy determination for the president, especially from a spiritual, sci-
entific, and political standpoint. Describing the issue as "one of the most pro-
found of our time," the president made his final decision after meeting with his
1 4 7
THE GENETI CS REVDLUTI DN
top aides at his ranch in Crawford, Texas, telling them that the decision was as ag-
onizing as sending U.S. troops into combat: "It is important that we pay attention
to the moral concerns of the new frontier. I have made the decision and I pray it
is the right one."
3
Ari Fleischer, at the time White House Press Secretary, told an audience that he
believed the president made the right decision: "This is a very sensitive issue that
divides American society. It involves the promise of life and the destruction of life.
The President made a principled decision that he stands proudly behind. Progress
will be made without destroying life. The President and his administration support
alternative routes to obtain stem cells, including use of adult cells. So, in effect, the
President's decision was a compromise. President Bush has made it clear that
cloning humans is 'morally wrong' and we should not create life to destroy it."
4
President Bush repeatedly assured conservatives that he would never permit
federal funding of stem-cell research that required the destruction of human em-
bryos. In addition to his belief that life begins at conception, the president em-
phasized that he opposes abortion and that he believed destruction of embryos
for stem-cell research is the same as ending human life by abortion. This position
is also held by the Roman Catholic Church. Repeating his decision, the president
said that he would allow funding for research on existing stem-cell lines, but
would not allow funding for the creation of additional stem-cell lines from exist-
ing or future human embryos because it involved extraction of stem cells from
embryos and subsequent destruction of embryos.
Considerable Input
President Bush consulted many individuals and groups and read widely before
reaching his decision. Ethicists, physicians, religious leaders, abortion foes, law-
makers, and health activists offered their views to the president. For several
weeks prior to making the decision, three of President Bush's top aidesSecretary
of Health and Human Services Tommy Thompson, Chief of Staff Andrew Card,
and political advisor Karl Rowe worked to help the president find a solid com-
promise, one that would please both the pro-human-embryo-research commu-
nity and those opposed to human embryo cloning.
Leading up to the president' s decision, leading conservatives had urged him
to reject any kind of funding for embryonic stem-cell research. Nancy Reagan,
wife of former President Ronald Reagan (an Alzheimer's victim) sent word to the
Whi t e House that she supported embryonic stem-cell research, although as an
opponent of abortion, she also supported former President Reagan's value of hu-
man life and the need to protect it at all stages.
On behalf of Nancy Reagan, former Reagan aides Kenneth Duberstein and
Michael Deaver delivered a message to then U.S. House Speaker Dennis Hastert
and U.S. Senate Republican leader Trent Lott: "This would mean an awful lot to
Nancy, especially for a cure for Alzheimer's, even if it's not for the President, but
for future generations."
5
However, President Bush's final decision to allow funding for limited embry-
onic stem-cell research was shaped by, more than anyone else, Leon Kass, a
1 4 B
A MA JDR DECI SI DN
University of Chicago bioethicist. Earlier, Bush had named Kass to head a Whi t e
House Commission to oversee stem-cell research and set practical guidelines.
Sharing the president' s views, Kass is an opponent of human cloning who also
shared the president' s concern that research on embryonic stem cells needs rigid
controls. "Anyone truly serious about preventing human reproductive cloning
must seek to stop the process from the beginning, at the stage where the human
somatic cell nucleus is introduced into the egg."
6
In formulating his decision, President Bush kept returning to two fundamen-
tal questions: "First, are these frozen embryos human life and therefore some-
thing precious to be protected? Second, if they' re going to be destroyed anyway,
should they be used for a greater good, for research that has the potential to save
and improve other lives?"
7
President Bush had repeatedly said that he believed that killing to cure is
morally repugnant and must not be established in law and that people, no matter
their age or stage of life, are not products to be used for the benefits of others, no
matter how noble the intentions. In effect, the president said that he believed that
even the most noble acts do not justify any means.
Prior to making his decision, the president met with Pope John Paul II on
Monday, July 23, 2001, at the pope' s summer retreat (Castel Gandolfo) in the
foothills southeast of Rome. During the meeting the Pope denounced embryonic
stem-cell research, telling the president that destroying embryos to obtain stem
cells amounts to ending a life: "A free and virtuous society, which America as-
pires to be, must reject practices that devalue and violate human life at any stage
from conception to human life. Experience is already showing how a tragic coars-
ening of consciences accompanies the assault on innocent human life in the
world."
8
During the same meeting, the pope also repeatedly denounced euthana-
sia, infanticide, and proposals for the creation of human embryos for research
purposes.
The president' s own United Methodist Church previously pleaded with him
to use extreme caution in proceeding with activities that would result in the de-
struction of human embryos. In support of human embryonic stem-cell cloning,
eighty Nobel laureates sent the president a letter urging federal funding for re-
search that could produce novel therapies for a range of serious and currently
intractable issues. Other supporters of embryo donation (embryo adoption) of-
fered it as an alternative to embryo destruction.
President Bush also carefully reviewed past legislation and action taken with
regard to embryo research and noted that in 1979 with bipartisan support, Con-
gress had approved a moratorium on experiments using human embryos fertil-
ized in laboratories. Also, in 1985 Congress had denied funds for experiments
that had the potential to do harm to embryos in the womb.
In 1994 President Clinton' s Commission on Stem-cell Research recom-
mended caution but suggested that stem-cell research held great potential to cure
disease. At that time, the Clinton administration allowed federal money for stem-
cell research as long as embryonic cells were extracted with private money rather
than with federal funds.
During this time legislators also became involved. Representative Jay Dickey
(R-Ark.) sponsored the first Dickey amendment, which was added in 1996 to a
l 4 9
THE GENETI CS REVDLUTI DN
House appropriations bill. The amendment banned federal funds for experi-
ments that destroy human embryos. Current law (The Dickey Amendment, in
Public Law 106-554) prohibits federal funding of any research in which human
embryos are destroyed, discarded, or knowingly subjected to risk of injury or
death. The law embodies the principle that nonconsenting human beings must
not be subjected to harmful medical experimentation.
In 1998 researchers at the University of Wisconsin (WiCell Research Institute
Inc.) and at Johns Hopkins University in Baltimore, using federal funds, extracted
and grew stem cells from human embryos. The five stem-cell lines developed by
Wicell were offered to the National Institutes of Health (NIH) for research pur-
poses. The agreement stipulated that NIH scientists be allowed to publish freely
and retain ownership of any new intellectual property that resulted from stem-cell
research. A Memo of Understanding (MOU), a "Simple Letter of Agreement,"
governed the transfer of cell lines to individual laboratories with minimal admin-
istrative burden. WiCell retained commercial rights to the stem cells, as well as a
fee to cover the handling and distribution expenses in supplying the cell lines.
9
In the year 2000, at the prompting of the Clinton administration, officials
at NIH agreed to fund stem-cell experiments, provided that the embryos were
created without government funding; supporters of the Dickey amendment
protested. In February 2001, President George W. Bush attempted to reverse pol-
icy by ordering a review of guidelines issued by President Clinton that would
have allowed spending taxpayer money on stem-cell research. After a complete
review, President Bush halted all NIH-funded stem-cell research.
In July 2001, Advanced Cell Technology (ACT), a private research firm, an-
nounced that it had created embryos for stem-cell research using private funds.
ACT had approached donors and informed them that their eggs and sperm
would be used to develop embryos for stem-cell research. That same month, the
U.S. House of Representatives banned cloning of human beings to create stem
cells for research. Senator Bill Frist (R-Tenn.), Senate Majority Leader, suggested
a plan that would ban the creation of embryos for stem-cell research but would
permit federal funding for experiments on excess embryos from fertility clinics.
Frist's plan was in direct contrast to a rival plan by Health and Human Services
Secretary Tommy Thompson, which would fund only research that used existing
stem-cell colonies.
Reactions to President Bush's Decision
President Bush's decision to allow limited federal funding for existing human em-
bryonic stem-cell research won mixed reviews, outraging some abortion oppo-
nents and leaving many lawmakers and scientists dissatisfied. Those who hoped to
be helped by stem-cell cloning said that the president's opposition to stem-cell
cloning was misplaced and totally unfair. However, the president defended his de-
cision, saying that it was a compromise between the sanctity of life and the ur-
gency of stem-cell research that meant hope to those who battle serious diseases.
10
After thoroughly studying the human embryo cloning issue, the president
said that the embryo cloning process would require "massive" numbers of
1 5 D
A MA JOR DECI SI DN
women' s eggs, potentially turning women' s bodies into commodities and creat-
ing a national market for women' s eggs. In further defending his proposal, the
president argued that once cloned embryos were created for research, it would be
"virtually impossible" to prevent a scientist from implanting an embryo in a
woman who was willing to carry the clone to term.
11
White House spokesman Scott McClellan said that the president made his
decision based on what he believed was in the best interest of the American peo-
ple. Supporting the president, Scot Red, a Republican strategist, argued that
Bush had succeeded in finding the right balance in his decision. Red said that the
decision would not unduly alienate the president' s conservative base, and would
in fact appeal to some moderate voters. However, abortion opponents in the Re-
publican party criticized the decision as a "bitter loss" because the president did
not ban embryonic stem-cell research altogether.
Roman Catholic leaders were dismayed with the president' s decision, saying
it had gone too far. Houst on Bishop Joseph A. Fiorenza, president of the U.S.
Conference of Catholic Bishops, was particularly harsh in his condemnation of
the president's decision: "The trade-off he has announced is morally unaccept-
able: the federal government, for the first time in history, will support research
that relies on the destruction of some defenseless human beings for the possible
benefit to others."
12
The bishop said he opposed the president' s decision primarily because exist-
ing stem-cell lines were obtained through the destruction of human embryos:
"We consider the stem cells that are now in possession to be what we could com-
pare to ill-gotten goods. For the government to allow funding for this experiment
makes the government complicit in what we consider to be wrongdoing."
13
The American Life League took out a full-page newspaper ad that likened
President George W Bush's promise on stem-cell research to the elder Bush's
"Read my lips: no new taxes" pledge in the 1988 campaign. Surprisingly, Christ-
ian Coalition founder Pat Robertson said he was satisfied with George W Bush's
plan because there was no killing of new life. Robertson, who has always opposed
abortion, said he favored the research using existing stem-cell lines: "It is just a
practical reality that this is a very useful science that has been held up because the
desire of all of us to prevent the destruction of human life."
14
The National Right to Life Committee, an antiabortion group that strongly op-
posed embryonic stem-cell research, said it mourned the embryos already destroyed
by stem-cell research and issued the following statement: "We are delighted that
President Bush's decision prevents the federal government from becoming a
party to the killing of any further embryos for medical experimentation."
15
The Church of Jesus Christ of Latter-day Saints is neutral on the subject, al-
though it opposes abortion as unjustified killing except possibly in cases of in-
cest, rape, or serious peril to the mother.
The Uni on of Ort hodox Jewish Congregation favors stem-cell research if it
involves frozen embryos that are left over from test-tube baby treatments. Jewish
religous law places high value on the principle that everything possible must be
done to save lives.
In Islam, many jurists accept work with embryos to seek medical therapies.
The Religious Coalition for Reproductive Choice advocates full access to
l 5 1
THE GENETI CS REVDLUTI DN
abortion on behalf of mainline Protestants, Conservative and Reform Jews, Uni-
tarians, and others. The coalition believes the medical potential justifies research
that employs the test-tube leftovers or aborted fetuses. However, they are con-
cerned about programs that create cloned human embryos in order to destroy
them and acquire stem cells. This is morally problematic for the coalition.
The California Council of Churches supports a state program that involves
stem cell harvesting through destruction of cloned embryos.
On the opposite side of the religious spectrum, the Roman Catholic Church
teaches that the life of every human being is to be respected once a sperm and egg
unite. It vehemently opposes destroying embryos, whether through abortion or for
research. Eastern Orthodox and evangelical Protestant churches generally agree.
Adding further support for President Bush's decision, Tommy Thompson, a
Roman Catholic and secretary of Health and Human Services, stated that the pres-
ident's decision was moral because it allowed federal funding only on embryos
that had already been destroyed. Thompson issued the following statement:
President Bush opened the door to embryonic stem-cell research in an
ethical and morally sound manner. The immediate challenge for us is to
conduct the vital basic research. Before we can talk credibly about ther-
apies for diseases, we must do the fundamental research to fully under-
stand how those cells work. This basic research will take years, but can
now occur with federal funding with an adequate supply of lines. There
is value in research at all stages. Very valuable basic research can be
done on stem cells at all stages of development. Researchers will now
be able to use federal dollars to work on further developing some of
the existing lines. We need to get to work. We have a historic opportu-
nity for research that did not exist at this level until now. Although we
certainly want to seize the moment, we must not lose sight of the fact
that the research we do must be conducted in an ethical manner. The
only place we're going to find definitive answers to all of these ques-
tions is in the laboratory. The lab door is now open; let's get to work.
16
Most of the president' s supporters praised his decision as a reasonable,
statesman-like compromise for stem-cell research. However, others who sup-
ported the president' s decision believed it was motivated by his deeply-held per-
sonal and religious beliefs, in addition to his political beliefs.
At a July 19, 2001, news conference with British prime minister Tony Blair,
President Bush referred to stem-cell cloning when he announced: "This is way be-
yond politics. This is an issue that speaks to morality and science and the juxta-
position of both."
17
The president' s decision on human embryonic stem-cell research also af-
fected many lawmakers personally. Although some key lawmakers were encour-
aged by the decision to allow federally funded embryonic stem-cell research,
others expressed concerns that it failed to meet scientists' needs. Senator Edward
Kennedy (D-Mass.) issued the following statement: "Restrictions on this life-
saving research will slow the development of the new cures that are so urgently
needed by millions of patients across America."
18
l 5 2
A MA JOR DECI SI ON
Senate Majority Leader Tom Daschle (D-S.D.) and Senator Patrick Leahy
(D-Vt.) reported that, while they opposed human cloning, they would support
human embryonic stem-cell research. Senator Daschle issued the following state-
ment: "I support cloning for research purposes, but we vehemently oppose any
cloning for purposes of human replication."
19
Dan Perry, executive director of the Alliance for Aging Research, a Washing-
ton advocacy group for research on aging, said that the president' s decision, al-
beit important, fell far short of what researchers and suffering patients really
need. After hearing the president' s decision, Perry said that patient advocacy
groups regarded the decision not as the end of the debate but as the beginning of
a new battle.
Many believed that human embryonic stem-cell research had been taken
from behind the walls of private laboratories and placed in the public spotlight
for the first time. There was also fear that without federal funding, stem-cell
research would be developed solely by private companies lacking necessary ethi-
cal safeguards. Others were concerned that without public funding in the United
States, human embryonic stem-cell research would progress at a snail's pace or be
driven overseas.
How Many Stem Cell Lines?
Prior to the president' s August 9, 2001, decision, controversy intensified over the
number of available stem-cell lines that researchers had to work with. Aware of
wide differences in the scientific community as to how many stem-cell lines ex-
isted, the Whi t e House asked Secretary of Health and Human Services Tommy
G. Thompson, to contact the National Institutes of Health (NIH) and ask for
their help in conducting a worldwide survey to determine the number of avail-
able stem-cell lines.
In response to the president' s request, NIH researchers cataloged a Human
Embryonic Stem Cell Registry of stem cell lines existing worldwide and reported
to the Whi t e House that it had found at least sixty "genetically diverse" cell lines
(possibly as many as sixty-five), with about thirty of them in the United States.
Based on the NIH finding, Tommy Thompson reported back to the president and
his administration that the world' s supply of available human embryonic stem-
cell lines would be adequate to allow scientists to conduct effective embryonic
stem-cell research: "The President's decision balances our deepest respect for life
but also our highest hopes for alleviating human suffering. But the decision has
spawned the question of whether the existing stem-cell lines are adequate to con-
duct effective research. The more than 60 stem-cell lines are diversely robust and
they' re viable for research."
20
However, leading scientists continued to dispute the number of stem-cell lines
in existence and available to researchers. Most argued that even if there were sixty
or more cell lines the number would, in no way, be sufficient to treat a diverse
population of patients. The reason, scientists pointed out, was that while there
may be that many cell lines available today, tomorrow there may be significantly
fewer because most cells are unstable over a long period due to contamination.
l 5 3
THE GENETI CS REVOLUTI ON
Convinced that the NIH cell-line numbers were accurate, the president re-
ported to the nation that there existed at least sixty genetically diverse stem-cell
lines and that there would be enough cell lines to explore the promise and poten-
tial of stem-cell research without crossing a fundamental moral line.
21
However,
many scientists did not believe the president and thought instead that only a
small number of cell lines were on the federally approved list and available to ac-
ademic researchers. One such scientist was Ronald McKay, a senior investigator
at the NIH in Bethesda, Maryland, who said: "Just because the President says
something doesn' t mean it happens tomorrow. It actually takes time to grow
these cells. Good science takes time."
22
Defending the president, Whi t e House spokesman Ari Fleischer argued for
the availability of stem cells, saying: "This is a new field, and it is unreasonable to
expect instant action on something that is so promising, so untested and so new.
What ' s important is that progress is being made and will be made."
23
Following President Bush' s announced decision and, given the uncertain
number of stem-cell lines, the American Association for the Advancement of
Science (AAAS) issued a statement asking for disclosure of the exact number and
sources of existing cell lines. The AAAS also requested information about the
ownership and intellectual property status of the cell lines. They asked that the
cell lines be released for evaluation so that it could be determined whether the cell
lines could be accessed freely for future research and possible medical use.
On September 5, 2001, amid growing skepticism, Health and Human Ser-
vices Secretary Tommy Thompson admitted that a mistake had been made and
that fewer than thirty cell lines were available for stem-cell research, not nearly
enough to ensure the wide-ranging research that President Bush had promised in
his speech on August 9, 2001. Some called it a deliberate lie on the part of the
Bush administration; others called it shoddy research on the part of the NIH.
Whatever the reason, because of the limited number of cell lines many sci-
entists felt that eventually researchers would run short on research materials,
sending prices skyward. Art hur Caplan, bioethicist at the Center for Bioethics at
the University of Pennsylvania, agreed that prices would probably rise, saying:
"There' s nothing to stop them from charging what they want. And, worse, they
can add conditions demanding a share on any discovery or therapy made down
the road. This compromise threatens to push stem-cell work far into the private
sector."
24
Calling for public funding, Caplan said he believed that private research
would continue in "uncontrollable Wild West fashion" unless more funding
from public sources was allowed.
25
National Academy of Sciences Report
A September 17, 2001, report from the National Academy of Sciences (NAS), an
independent panel of experts that advises the president, suggested that the stem-
cell research program that President Bush approved was not sufficient to produce
significant results. In the NAS report, scientists declared that not allowing new
stem-cell line development could result in inferior research. The NAS report in-
dicated that a large amount of work remained before treatments could be devel-
l 5 4
A MA JOR DECI SI ON
oped and encouraged researchers to aggressively pursue stem-cell work. This an-
gered opponents of stem-cell research and bolstered critics who said that the
president' s plan did not go far enough.
Most scientists agreed that the number of available cell lines was insufficient
and that only by studying hundreds of embryonic cell lines could universally avail-
able treatments be developed. They pointed out that the low numbers of available
stem-cell lines (less than thirty) actually available meant that the genetic diversity
of the cells would be severely curtailed. Diversity is considered essential to de-
velop treatments for millions of patients, each with a unique genetic structure.
Harold Varmus, former director of the NIH and at the time head of the Memor-
ial Sloan-Kettering Cancer Center, made it known that it would be a very cruel in-
vestment if scientists learned to grow cells for transplantation but did not have
access to enough cell lines to treat patients effectively.
The president' s decision did not allow new supplies of stem cells to be gener-
ated using public funds nor did it encourage him to revisit his decision to limit
federal funding for embryonic stem cell research, according to Health and Hu-
man Services Secretary Tommy Thompson: "The president will not equivocate.
He made a very strong statement on that."
26
Thompson also said that the presi-
dent believed basic research should continue before any legislation was sought to
allow broader federally financed embryonic stem-cell research.
On April 10, 2002, the president conducted an East Room ceremony at the
White House promoting the anticloning bill. He continued to press the U.S. Sen-
ate to ban cloning of human embryos for research, saying science must not rush
ahead without an ethical compass. "We can pursue medical research with a clear
sense of moral purpose, or we can travel without an ethical compass into a world
we could live to regret. How we answer the question of human cloning will place
us on one path or the other. Life is a creation, not a commodity."
27
In late April 2002 the biotech lobby mobilized in Washington to fight anti-
human-cloning legislation. At this time a survey of 800 adults by the The Polling
Company showed 63 percent of the populous totally agreeing with President
Bush' s strong anticloning statement and 29 percent disagreeing. Sixty-eight per-
cent of women agreed with the president as compared to 53 percent of men.
An Ethical Compass
Politicians rose to the occasion. Senator Mary Landrieu (D-La.) and Senator Sam
Brownback (R-Kans.) cosponsored an anticloning bill titled the Human Cloning
Prohibition Act of 2003 (S.245). In turn, President Bush solicited support for the
Brownback/Landrieu bill. U.S. Senator Bill Frist (R-Tenn.), a highly respected
heart-transplant surgeon and Senate Majority Leader, issued a statement in sup-
port of the Brownback/Landrieu ban on human cloning: "Once cloned embryos
are available, implantation will take place. Even the tightest regulations and strict
policing would not prevent or detect the birth of cloned babies."
28
However, late
in July 2005 Frist endorsed government-funded research on human embryonic
stem cells, breaking with President Bush and the religious conservatives.
In speaking against the Brownback/Landrieu bill, Senator Edward Kennedy
l 5 5
THE GENETI CS REVDLUTI DN
(D-Mass.) issued the following statement: "We must not let the misplaced fears of
today deny patients the cures of tomorrow. Congress was right to place medicine
over ideology in the past, and we should do the same again as we confront the is-
sue of cloning."
29
Other senators also voiced opposition to the ban on human embryo cloning.
Senator Arlen Specter (R-Pa.) said that he believed a ban on human embryo
cloning would criminalize legitimate research, tie the hands of medical science in
the twenty-first century, and cause an enormous brain drain out of the United
States to Europe.
30
Senator Tom Daschle (D-S.D.) urged lawmakers to listen to
forty Nobel laureates who supported cloning research.
31
Senators Dianne Feinstein, Ted Kennedy, Orrin Hatch, Arlen Specter, and
Tom Harkin also introduced a bill, the Human Cloning Ban and Stem Cell Research
Protection Act of 2003. The Christian Legal Society (CLS) called on the U.S. Sen-
ate to defeat the Feinstein/Hatch Act and instead enact the Landrieu/Brownback
bill. The CLS, founded in 1961, is a national membership organization of nearly
3600 Christian attorneys, judges, law professors, law students, and supportive lay
people. The major difference between the two bills is that the Feinstein/Hatch bill
would allow therapeutic cloning while the Landrieu/Brownback bill would crimi-
nalize certain types of promising medical research.
In May 2005 the U.S. Congress debated several stem cell research bills. Presi-
dent Bush has threatened to veto any bill that involves the use of cloned human
embryos, no matter how they are produced. The U.S. House approved one bill by
a vote of 238 to 194, far short of the two-thirds majority that would be needed to
override a veto.
An alternative offered by Republican leaders that would fund research using
stem cells derived from adults and umbilical cords rather than from embryos
passed 430 to 1, with Representative Ron Paul (R-Tex.) the lone opponent.
A more controversial bill, sponsored by Representatives Mike Castle (R-Del.)
and Diana DeGette (D-Colo.), would lift President Bush's 2001 ban on federal
funding for new research using stem cells from embryos that had not been de-
stroyed before August 2001. The House vote on the Castle-DeGette bill was in-
tended mostly on a show of force to help propel it through the Senate and, the
sponsors hope, into compromise talks with the White House. The Castle-DeGette
bill deals with embryonic stem cells.
Representative Chris Smith (R-NJ.) believes that there are other ways to get
where we want without cloning and using human embryos or aborted babies. In
May 2005 he introduced a bill called the Stem Cell Therapeutic and Research Act
of 2005. The bill would create a national program that would use cells from um-
bilical cords. Umbilical cord transplants have proved effective for treating pa-
tients suffering from inherited immune diseases like sickle-cell anemia and
leukemia, even when those transplants are from unrelated donors. In August
2005, Harvard scientists announced that they had discovered a way to fuse adult
skin cells with embryonic stem cells, a breakthrough that could lead to all-
purpose stem cells. These cells could be created without harming embryos. In ef-
fect, embryonic stem cells could reset adult cell genes through the cell fusion.
1 5 6
PART V
To Clone or Not to Clone:
That Is the Question
On July 5, 1996, Drs. Ian Wilmut and Keith H. S. Campbell cloned Dolly the
sheepthe first large creature ever cloned from a differentiated adult cell. The
remarkable breakthrough was heralded as one of the most significant scientific
accomplishments of the twentieth century. Now, there is the expertise and tech-
nology to clone a human. Cloning of humans is at an ethical and moral cross-
roads, and most scientific inquiries and bioethical conversation about human
cloning are on the subject of pro-life politics and religion. The fundamental con-
cern centers around the moral status of the embryo.
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ID
REPRODUCTIVE CLDNING
Three cloned mice,
Three cloned mice,
See how they run,
See how they run.
They all ran after the scientist,
Who cut them out of a blastocyst.
Did you ever think such a thing could exist
As three cloned mice?
Bernard Mergen, Washington Post,
Sunday, January 11, 1981
In January 1981 it was announced publicly that three healthy mice had been
cloned. After seeing the story in the New York Times on January 4, with its head-
line "Three Mice Cloned in a Laboratory," Bernard Mergen, a professor of
American Civilization at George Washington University in Washington, D.C.
wrote the above rhyme.
Dr. Peter Hoppe of the Jackson Laboratory in Bar Harbor, Maine, and
Dr. Karl Illmensee of the University of Geneva were the scientists who allegedly
cloned the mice by transplanting the nuclei of mouse embryos into mouse eggs.
However, when other scientists tried to duplicate the experiments, they found
that the cloning results could not be replicated. Rather than all three mice being
produced from the same embryo, it was discovered that the three mice came from
three different embryos.
Following public announcement of the mouse experiment, leading scientists
called for a ban on human cloning, asking: if cloning is successful in mice what is
THE GENETI CS REVOLUTI ON
to stop someone from trying it on primates, and then on humans? Today, cloned
mammals include mice, pigs, primates, sheep, cattle, and horses, as well as humans.
Cloning Not New
The word "cloning" makes people nervous. Yet, cloning is not new. It has been
going on the natural world since the beginning of time. Because there is nothing a
priori unnatural about cloning many say there are no scientific grounds per se to
ban cloning. Others disagree.
More clones are present in the world than one would imagine. For example, in
nature there are clones that everyone is familiar withplants and algae, some in-
sects, and certain unicellular organisms that conduct mitosis or binary fission.
Amoebas clone themselves when they divide. Interestingly, the armadillo litter
is always a batch of eight octoplets, an eight-clone. Earthworms cut in half have
the ability to regenerate the missing parts of their bodies, resulting in two distinct
worms with the same set of genes in each clone-twin. Plants clone themselves
when they reproduce by budding or by sending up new shoots. All human tissue
is potentially a source for cloning and some tumors are considered clones, derived
from one aberrant cell that no longer obeys the normal rules of growth control.
Human Clones
When most people hear the word cloning, the first thing they think of is human
reproductive cloning (duplicating babies). Most people are opposed to that type
of cloning, yet in the strict sense biological human clones, for example identical
twins, have existed as long as humanity itself. Human monozygotic twins are nat-
ural clones of each other, splitting from a single embryo. With individual charac-
ters, they have the same exact genetic information due to the division of the
embryo early in development. Because sex is the normal means by which new ge-
netic material is introduced during procreation, clones have the same genes as
their single parent.
1
At least 8 million identical, or monozygotic, twins are alive in the world. Some
consider identical twins as one person born with two bodies. As identical twins,
clones have individual differences, separate identities and separate souls. Natural
twins are much more alike than clone-twins because natural twins are exactly the
same age, whereas a clone-twin and the DNA donor may be decades apart in age.
In effect, a clone-twin is a time-delayed identical twin of another person.
Whet her produced naturally or artificially, clones are identical only physi-
cally because human selves, unlike human cells, can never be cloned. Environ-
mental influences render them different, sometimes even before birth. "If clones
are simply identical twins by another name, there is no reason to believe they will
be any more similar than such twins are. In fact, because clones and their adult
forebears would be born into different generations from different wombs, and
have different arrays of environmental choices, there is every reason to think they
will be even more different from each other than identical twins are."
2
1 6 0
REPRODUCTI VE CLONI NG
Some scientists have considered experiments that combine human genes
with animal genes to make a half-and-half breed. Geep (half sheep and half
goat) have already been born. Combining humans and monkeys, to make a
half-and-half breed called a humonkey, would not be difficult (although not
desirable), requiring the combination of two balls of growing cells in the pre-
embryo stage. The genetic code for primates (including chimpanzees and mon-
keys) and humans is 99 percent identical, which means that less than 1 percent
of the code determines individual differences. Because primates and humans
share most of their genes in common, theologians frequently pose the follow-
ing questions:
Would humonkeys be able to receive salvation like humans?
Would humonkeys be recognized as morally responsible individuals before the
law if they were able to talk?
Recently, scientists have fused rabbit eggs with human DNA, used human
stem cells to make paralyzed mice walk, and created pigs with human blood.
But the co-mingling of animal and human cells is now becoming of more con-
cern, particularly with the mixing of brain cells. The question arises, What if
human brain cells (neurons) were found in brains of nonhuman species? Does
this mean the human mind could be contained within the sheep' s brain?
Charles Darwin, in his book The Expression of the Emotions in Man and Ani-
mals, cites one of "Father of Eugenics" Sir Francis Galton' s anecdotes:
A gentleman of considerable position was found by his wife to have
the curious trick, when he lay fast asleep on his back in bed, of raising
his right arm slowly in front of his face, up to his forehead, and then
dropping it with a jerk so that the wrist fell heavily on the bridge of his
nose. . . . Many years after his death, his son married a lady who had
never heard of the family incident. She, however, observed precisely
the same peculiarity in her husband; but his nose, from not being par-
ticularly prominent, has never as yet suffered from the blows. One of
his children, a girl, has inherited the same trick.
3
It seems there may be more in our genes than we often realize.
Kinds of Cloning
There are several different kinds of cloning which involve three distinct paths:
adult-cell (somatic or body cell) cloning, natural and artificial embryo cloning,
and stem-cell (therapeutic) cloning. In adult-cell cloning the development of an en-
tire animal such as Dolly the sheep is obtained from a single body (somatic) cell,
other than an egg or sperm, of another animal. In the first step of somatic cloning
the nucleus of an egg (ovum) containing the maternal genes is removed (enucle-
ated). Next, DNA from a cell from the individual to be cloned is implanted into
l 6 1
THE GENETI CS REVOLUTI ON
the empty egg, creating a cell with a perfect set of genes. The egg is activated in a
manner similar to natural fertilization, allowed to develop into an embryo, im-
planted into the womb of a female for further development into a fetus, and al-
lowed to develop to a full-term baby.
In natural embryo cloning an egg and a sperm are joined in vivo (in the body)
and allowed to grow and divide in the body. In the laboratory, artificial (deliberate)
embryo cloning begins with joining a sperm and an egg in a petri dish (in vitro fertil-
ization) to form a fertilized egg called a zygote. After union, there is a natural di-
vision of the zygote; normal cell division occurs into two, four, eight cells, etc. If
an egg splits, identical twins are the result.
In stem-cell (therapeutic) cloning an embryo is deliberately created in order to
obtain and use its stem cells. Stem cells are coaxed into replicating into any de-
sired tissue or organ in the body and have great potential in treating persons suf-
fering from diseases such as Alzheimer's, Parkinson's, and cancer.
Some believe that cloning is simply an extension of in vitro fertilization, but
although there are many similarities, cloning goes beyond that. Cloning, like in
vitro fertilization, takes the same type embryo and destroys its originality through
duplication. There is no doubt that research on in vitro fertilization has helped to
improve cloning techniques.
A Brief History of Cloning
The first attempts at artificial cloning were as early as the late 1890s and were
exercises in artificial twinning. By splitting the embryos of frogs, sea urchins, sala-
manders, fish, and other animals, scientists found that they could produce addi-
tional embryos that would develop into small but otherwise normal larvae.
However, scientists discovered that the technique worked only at a very early
stage of development, when the fertilized egg had divided into no more than eight
cells. Beyond the eight-cell stage (and sometimes even before), cloning failed, pri-
marily because each of the subdivided cells contained too little cytoplasm, the
material surrounding the nucleus.
4
In the late 1890s Adolph Eduard Driesch let the eggs of a sea urchin develop
into the two-blastomere stage, separated the blastomere by shaking the flask, and
allowed the cells to grow. Driesch selected sea urchins because they had large em-
bryo cells and grew independently of their mothers. Eventually, the cells devel-
oped into whole dwarf sea urchins. His original goal was not to create identical
animals, but to prove that DNA was not lost during cell division. At the time,
Driesch could not explain his experiments, became discouraged, and gave up em-
bryology for philosophy.
In 1902 the German embryologist Hans Spemman used a thin hair taken
from his blonde son, who was less than nine months old, as a knife to separate an
eight-celled salamander embryo. Later, he isolated a single cell from a sixteen-
celled salamander embryo. In each experiment, both the large and small embryos
developed into identical adult salamanders. In removing the DNA from an adult
cell, Spemman used the DNA to grow another adult salamander, theorizing, as
had Driesch, that no DNA was lost as cells grew and divided.
1 6 2
REPRODUCTI VE CLONI NG
The first successful implantation of a nucleus into an egg occurred in 1952.
Robert Briggs, a zoologist at Indiana University, and Thomas J. King of the Institute
for Cancer Research and Lankenau Hospital Research Institute (now known as the
Fox Chase Center) in Philadelphia, described a way of transferring a nucleus, and
with it the DNA, of a leopard frog's (Rana pipiens) embryo, into another Rana egg.
The procedure, called nuclear transplant, involved taking an immature frog cell, at a
late stage of its development (before it began the final round of divisions that pro-
duce mature eggs), and pricking it with a glass needle to activate its first division cy-
cle. With another glass needle, the egg's nucleus was removed microsurgically.
Next, Briggs and King took the blastula, an early embryonic stage of another
frog, and sucked up one of its cells with a micropipette. After breaking the cell's
membrane, they injected the ruptured cell onto the top of the enucleated egg. The
scientists transplanted the entire cell containing both the nucleus and the cyto-
plasm because they considered the nucleus too fragile to survive the procedure on
its own. The cytoplasm of the egg cell "reprogrammed" the new blastula nucleus,
resetting its genes so that they functioned as original genes of the egg cell. The nu-
clei from the undifferentiated cells came from late-stage blastulas, hollow balls of
cells. Each frog egg cell, with a full set of chromosomes, began to divide and form
normal embryos that developed into normal tadpoles and normal young frogs.
Today, modern developmental biologists consider this procedure cloning.
Briggs and King chose frogs to use in their experiments because frog eggs
were more abundant and much larger than those of mice, sheep, or humans. Be-
cause frog embryos were easy to rear (all a fertilized egg needed was a dish of wa-
ter), they developed in the open with their early divisions in plain view. All Briggs
and King's experiments began with embryonic cells (undifferentiated) or cells
specialized for a particular physiological function.
In 1953 Briggs and King expanded their experiments to successfully transplant
nuclei from early-stage gastrula cells. A gastrula is a three-layered structure consist-
ing of the ectoderm (outer layer), the mesoderm (middle layer), and the endoderm
(inner layer). The scientists selected endodermal cells for their experiments because,
of the three germinal layers, the endoderm had the largest cells and was the easiest
layer to handle. Their experiments, however, produced many abnormal embryos.
Although Briggs and King worked with frog eggs and embryos, their ground-
breaking techniques paved the way for mammalian clonings, including Dolly the
sheep. In 1972 they were awarded the Charles Leopold Mayer Prize by the French
Academy of Sciences; they were the first Americans to receive the highest biol-
ogy award given by the academy.
In 1956 Dr. John Gurdon began graduate work at the University of Oxford,
England, under the supervision of developmental biologist Michael Fischberg.
Gurdon worked on nuclear-transplant experiments in %enopus laevis, the South
African clawed frog. In 1958 Gurdon teamed with Fischberg and Thomas R.
Elsdale to develop nuclear-transplant embryos in sexually mature Rana pipiens
adult frogs, demonstrating that the nuclei of cells that had undergone develop-
ment remained totipotent, not just pluripotent. In addition, the scientists were
also able to get normal development with much older donor tissue than had pre-
viously been reported with Rana.
5
In 1960 Gurdon reported that normal nuclear-transplant embryos, including
1 6 3
THE GENETI CS REVOLUTI ON
some that developed into feeding tadpoles, grew from endoderm cells of tail-bud
tadpoles, not just from the cells of gastrulas. He concluded from his work with
Xenopus that the specialization of cells was not necessarily accompanied by a loss
or deadening of gene expressiona conclusion that differed from the one reached
by Briggs and King.
6
Although Gurdon' s results proved puzzling at the time, work done by Marie
A. Di Berardino of the Medical College of Pennsylvania-Hahnemann School of
Medicine, Allegheny University of the Health Sciences in Philadelphia clarified the
situation. Di Berardino showed that all embryos that died before the feeding-
tadpole stage of development possessed visibly abnormal chromosomes and that
the more severe the developmental disorder, the more severe the prior chromoso-
mal defects. In addition, Di Berardino showed that the Xenopus nuclei or chro-
mosomes were more resistant to damage during transplantation.
7
In 1970 developmental biologist Sally Hennen of Marquette University in
Milwaukee, Wisconsin, added a protein called spermine to the nuclear-transfer
medium and performed the transplant at a lower temperature. She found that
this greatly improved the results of nuclear-transplant experiments with nuclei
from the endoderm of Rana pipiens.
8
In the early 1970s other scientists around the world became successful with
nuclear transfer experimentation. For example, scientists in France and Switzer-
land successfully cloned fertile fruit flies. At about the same time Chinese biologist
T. C. Tung and his successor Yan Shaoyi, both of the Institute for Developmental
Biology of the Academia Sinica in Beijing, conducted a series of successful experi-
ments with teleost fish.
In 1975 Gurdon, Ronald A. Laskey, and Raymond Reeves wrote a scientific
paper to which the Roslin scientists who cloned Dolly the sheep would refer
twenty-two years later. Gurdon, Laskey, and Reeves successfully injected the nu-
clei of skin cells (keratinocytes) from the foot webs of adult frogs and transferred
them into frog eggs from which the nuclei had been removed. Some of the in-
jected eggs developed into swimming tadpoles.
9
In explaining their experiment, Gurdon wrote:
We used skin cells from the adults' foot webs. When small pieces of
the foot web are cultured, a single layer of cells grows outward from
the excised tissue. We treated those monolayers with an antibody that
binds keratin, a protein made only by specialized cells, and we found
that 99.9 percent of the cells in the monolayers bound to the antibody,
thus revealing that they contained keratin. Nuclear-transplant experi-
ments done with those cells yielded heartbeat-stage tadpoles with well-
differentiated eyes and other organs. The probability that those clones
originated from the 0.1 percent of the donor-cell population unproved
to contain keratin was less than one in 10 billion. We felt justified in
concluding that "cell specialization" does not involve any loss, irre-
versible inactivation or permanent change in chromosomal genes.
10
Although all of Gurdon, Laskey, and Reeves's experiments fell short of
cloning an adult animal from the nuclei of cells derived from an adult animal, the
1 6 4
REPRODUCTI VE CLONI NG
scientists were able to conclude that cell differentiation did not involve any per-
manent or stable change in the chromosomes and that cell differentiation took
place though the controlled expression of genes. Later, they postulated that cell
differentiation was the foundation on which Dolly' s cloning stands, and it made
the cloning of other adult vertebrates possible.
A few years later, in the early 1980s, developmental biologists James Mc-
Grath and David Solter at the Wistar Institute of Anatomy and Biology in
Philadelphia cloned mice by fusing donor cells with mouse eggs. Based on prior
procedures for cloning frogs, their experiments included important innovations.
Following McGrath and Solter's experiments other laboratories around the
world began to t urn out impressive numbers of newborn mammals cloned from
embryonic nucleiamong them calves, rabbits, pigs, rats, goats, and lambs.
In 1983 Di Berardino and developmental biologist Nancy Hoffner Orr of the
Allegheny University of the Health Sciences transplanted donor nuclei into
oocytes (immature egg cells from the ovary), rather than into mature egg cells that
had already been released from the ovary. Di Berardino and Orr allowed nuclei
that had been transplanted into an oocyte twenty-four hours' exposure to the cy-
toplasm of the oocyte before cleavage. The success of their experiments was
attributed to the much longer time than nuclei transplanted into mature eggs.
This allowed the cytoplasm to reset the cell-division cycles. These techniques
led to transplantation successes with Rana comparable to those obtained with
Xenopus.
11
In 1984, embryologist Dr. Steene M. Willadsen, at the Agricultural and Food
Research Council Institute of Animal Physiology in Cambridge, England, an-
nounced that he had successfully cloned nuclei from early-stage sheep embryos.
Later, he cloned embryos that were in the 64-128 cell stage and suggested that
perhaps nuclear transfer might be possible with specialized (differentiated) cells.
A decade later, Dr. Neal First cloned four cows by nuclear transfer from more
developed embryos. These experiments, like those of Willadsen, began with un-
differentiated cells that had no particular physiological function. This was fol-
lowed by an experiment by Dr. Robert J. Stillman and colleagues at the George
Washington Medical Center in Washington, D.C. They publicly announced the
cloning of seventeen human embryos in order to encourage public discussion
about human cloning.
In July 1995 Scottish scientists Dr. Ian Wilmut and Dr. Keith H. S. Campbell
cloned two sheep named Megan and Morag from differentiated embryo cells.
Their new technique involved starving the donor embryo of the nutrient serum
they fed the cells. The advantage of this, they later ascertained, put the cell in the
right moment in the cell cycle, thus allowing the DNA to be accepted more easily
by the egg cell. This proved to be the essential step in nuclear transfer.
Hello, Dolly! Well, Hello Dolly!
On July 5, 1996, Wilmut and Campbell delivered lamb number 6LL3, or "Dolly,"
as she was named (after country music entertainer Dolly Parton), in a shed near
the Roslin Institute near Edinburgh, Scotland. Not a genetic mutant, Dolly was
1 6 5
THE GENETI CS REVOLUTI ON
the first large creature ever cloned from a specialized (differentiated) adult cell,
rather than an unspecialized embryonic cell.
Looking like a normal soft-eyed sheep, behaving like a sheep, and weighing
fourteen pounds, Dolly was described as a "beautiful lamb with a gentle disposi-
tion." With her typical sheep-like nose, she wandered around her cage and nuz-
zled photographers and visitors who came to view her. Dubbed the "lone clone,"
Dolly had no father, but she made up for it by having three mothersa nuclear
mother, an egg mother, and a womb mother. Roslin scientists had used three dif-
ferent breeds of sheep to produce Dolly as compared to one or two when in vitro
fertilization was used.
Wilmut and Campbell's remarkable breakthrough in producing Dolly grabbed
world headlines and was heralded as one of the most significant scientific accom-
plishments of the twentieth century. The cloning offered a new and unique way
of reproducing and genetically modifying animals. Interestingly, the visceral reac-
tion of the public to the announcement of Dolly's cloning was heralded by some
as more interesting than the scientific achievement itself.
12
Dolly was the world' s first successfully cloned adult mammal born to a sur-
rogate mother, cloned not from sex cells but from mature mammary cells with no
reproductive function. Using sophisticated microsurgery, Dolly was grown from
an egg cell whose nucleus had been replaced with DNA from mammary gland cell
of a pregnant six-year-old ewe. As a result, the recipient egg contained a complete
set of genes, just as it would had it had been fertilized by a sperm in the natural
process. Previously, it had been thought that a whole mammal could not be re-
generated from mature body (somatic) cells specialized for something other than
reproduction.
A nuclear marker present in the donor cell from which Dolly was cloned
showed that Dolly resembled the breed of the nuclear donor. Analysis of Dolly' s
DNA confirmed that Dolly was in fact the clone of her nuclear donor, a fact that
made Dolly immediately accepted by the scientific community as a valid clone.
13
Dolly was essentially her mother' s physical twin. However, scientists have
pointed out that even identical twins are not totally identical because not all of
the cell's DNA lies in the nucleus. Some DNA is also found in the cell's mito-
chondria ("powerhouses of the cell" that produce energy), which are found in the
cytoplasm of the cell. In reality, Dolly was an exact genetic copy or clone of the
sheep that provided the transferred nucleus, not of those that provided the egg.
Wilmut and Campbell started the Dolly cloning experiment with 434 sheep
oocytes. Because the procedure was very labor-intensive, it took 277 nuclear trans-
fers to produce Dolly. Of the original 434 oocytes, 157 failed to fuse with the trans-
planted donor cells and were discarded. The 277 successfully fused cells were
grown in culture, but only 29 embryos lived long enough to be transferred to sur-
rogate mothers. During gestation the investigators detected 21 fetuses with ultra-
sound scanning, but gradually all were lost except Dolly. With a success rate of only
one out of 434, it was clear that there were other unsolved complicating factors.
14
Another interesting fact was that frozen cells, not fresh cells, were used to
clone Dolly. This was a little known fact until after her birth and was significant
because it meant that the DNA donor need not be alive when cloning occurred
and the individual could be cloned long after birth. The Roslin experiment con-
l 6 6
REPRODUCTI VE CLONI NG
firmed that adult cells do in fact contain a workable version of all the genes nec-
essary to produce an entire organism.
In 1986 Wilmut had worked on a project to create a sheep that produced a
certain chemical in milk. In the experiment, he had altered cells and cloned them
to produce animals with altered genes all throughout their bodies. The experi-
mentation was extremely valuable and provided Wilmut and his team with the
needed techniques to clone Dolly. However, what really enabled Wilmut and his
team to succeed where so many others had previously failed was a simple modifi-
cation of prior techniques. Wilmut' s colleague, Keith Campbell, suggested that
the reason so many cloning experiments had failed was that the cells were in in-
compatible stages of life.
Eventually, both Wilmut and Campbell concluded that the key to their suc-
cess was in starving the mammary cells for five days and forcing the cells into a
kind of hibernation prior to removing their nuclei. They later determined that
this quiescent phase of the cell division cycle made the chromosomes more sus-
ceptible to the programming that initiates growth of a new organism. During this
time they realized that cellular differentiation was not a factor in cloning.
Wilmut and Campbell chose sheep for cloning because sheep proved more
easily cloned than mice or frogs. They realized that researchers had tried for de-
cades to clone frogs and mice with no luck. Generally, frogs cloned from adult
frogs died in the tadpole stage, whereas cloned mice did not develop far beyond
an undifferentiated ball of cells. Scientists concluded at the time that there was
just not enough time in the mouse' s lifespan for the extensive reprogramming of
gene activity that was required.
15
On April 13, 1998, Dolly became a mother when she gave birth to a healthy
lamb named Bonnie. Then, on Wednesday, March 24, 1999, Dolly gave birth to
three more healthy lambs, all conceived the "old-fashioned way."
Unexpectedly, in May 1999, Wilmut discovered that Dolly' s cells were six
years older than her chronological age. This meant that Dolly was over six
years old when she was bor n (the equivalent of a human being in her early thir-
ties). Dolly' s nuclear mot her was a six-year-old female sheep when the somatic
mammary cell was removed and placed in frozen storage in Wi l mut ' s labora-
tory.
Cells have an internal mechanism that keeps track of their age. It is thought
that in Dolly' s case the age mechanism of the donor cells was not reset to zero
when Dolly was conceived. This was of interest to many gerontologists who were
researching antiaging and progeria (a medical condition that causes infants to age
prematurely). After determining Dolly' s age, scientists asked:
Was Dolly really a six-year-old clone that at birth carried the DNA of a six-
year-old sheep?
Was Dolly' s secondhand DNA as good as new?
Was Dolly as old as her body age . . . or as old as her genes?
Several valuable pieces of new information were derived as a result of Dolly's
cloning. Scientists measured key pieces (telomeres) of Dolly's DNA and found that
l 6 7
THE GENETI CS REVOLUTI ON
the telomeres were shorter than those found in other three-year-old sheep, but the
same length as her mother' s. This suggested that Dolly was older than her birth date.
Another discovery was that Dolly' s nuclear DNA did not carry lethally dam-
aged genes. This was considered significant because it indicated to scientists that
in the future they might be able to take a person' s DNA and insert it into cells in
the laboratory, then grow tissue that could be transplanted back into that person
without the danger of rejection.
16
There were other lessons learned from the cloning of Dolly. For example,
Wilmut and Campbell showed that differentiated cells of one kind could be pro-
grammed to produce every kind of cell necessary for a complete organism. For
example, white blood cells (leukocytes) could be harvested and reprogrammed
into whatever cell type was needed.
17
It was also ascertained from Dolly' s cloning that cells taken from a young and
healthy person could potentially be stored for future production of replacement
organs should a person need them because of illness or old age. It became possi-
ble that an individual's own tissues could be used to grow replacement organs for
his or her own worn-out parts. This would be particularly useful to elderly or dis-
eased persons who needed tissue and organ replacement and who had not stored
their youthful tissues. However, such individuals would possibly not get much
benefit from cloned organs because such persons carry much more damaged
DNA in their cells than Dolly' s donors did.
18
Sadly, at the age of six, Dolly had to be euthanized after being diagnosed with
a virus-induced, slowly progressive lung disease. No treatment was available for
the disease. It was thought that Dolly contracted the disease from other sheep
that she was housed with. Dolly' s body was willed to the National Museum of
Scotland and has been put on display in Edinburgh. Scientists could not confirm
that her illness was attributable to being a clone.
Other Animal Clonings
Since the 1996 announcement of the cloning of Dolly, scientists worldwide have
duplicated and advanced the work of Wilmut and Campbell in a variety of
species. Credit also is given animal husbandry and agricultural research for the
many breakthroughs in animal cloning. As a result, there are now hundreds of
cloned animals; however, many more attempts have ended in failure.
19
Some ani-
mals have been cloned using slight variations in the technique used to clone
Dolly. Campbell and others from the Roslin Institute reported in 1996 that nuclei
from embryonic cells grown in culture created viable cloned lambs, making large-
scale production of genetically engineered animals and organs possible for the
first time.
20
On March 2, 1997, officials at the Oregon Regional Primate Research Center
announced that they had cloned sibling rhesus monkeys using cells from different
embryos. The cloning experiment proved that the technology for producing iden-
tical animals was now available. Don Wolf, senior scientist at the Oregon Regional
Primate Research Center, was cautious and did not call the procedure cloning, say-
ing: "That is not what I am calling it. Cloning in the strict sense of the word is us-
1 6 B
REPRODUCTI VE CLONI NG
ing an adult cell so you get an exact replica of the adult. That is not what we are do-
ing. The procedure called nuclear transfer can be done in humans."
21
In the Oregon experiment, scientists harvested eggs from a female adult mon-
key and fertilized each of the eggs in vitro. After three days, each embryo divided
into an eight-cell stage of development. Employing sophisticated microsurgery,
scientists teased apart the cells and removed one full set of chromosomes from
each egg cell, which they then inserted into each fresh egg that was enucleated.
Nine successfully developed embryos were then implanted in adult females. Of
these, three pregnancies and two live births resulted.
In another significant experiment on October 3, 1997, Cumulina, a mouse,
was cloned from cumulus cells (cells that surround developing egg cells). The nu-
cleus was taken from a cumulus cell and implanted in an egg cell from another
mouse. The new cell was then treated with a chemical to make it grow and divide.
Scientists repeated the process for three generations, yielding over fifty mice that
were virtually identical.
On February 20, 1998, the Korean Times reported that researchers at the
Seoul National University had successfully cloned a calf using methods identical
to those that produced Dolly. Korea became the fifth country in the world to
clone an adult animal after the United Kingdom, Japan, New Zealand, and the
United States. On July 22, 1998, Dr. Ryuzo Yanagimachi of the University of
Hawaii announced the cloning of seven out of twenty-two mice that were clones
from the cell of a single mouse.
Although scientists have been highly successful in cloning mice, they have
only recently overcome a quirk in rodent physiology that had thwarted many at-
tempts to genetically duplicate the rat. In the latter part of 2003, however, led by
researchers at the National Institute of Agricultural Resarch at Joy en Josas,
France, scientists cloned both male and female rats and then mated them and pro-
duced normal, healthy pups. This was hailed as exceptional research because
white laboratory rats with special genetic changes could be developed and used
for drug testing and other therapies to aid human patients. White laboratory rats
are among the most frequently used animal models for human disease research.
In producing the pups, scientists used a new technique called somatic cell nu-
clear transfer. Researchers first produced two male rat pups. In the second round
of cloning, they got two female pups. The pairs were later mated and produced
normal, healthy rats. The research is significant because it will enable researchers
to genetically tailor laboratory animals for studies of specific disorders that affect
humans.
Cloning Barnyard Animals
Following other numerous animal cloning experiments, Harold Shapiro, chairman
of the National Bioethics Advisory Committee, declared in November 1998 that
cloning research was rapidly progressing in a successful manner. On December 8,
1998, Japanese researchers from Kinki University in Nara, Japan, using techniques
similar to those that produced Dolly, cloned eight calves from a single adult cow's
DNA. However, four calves died shortly after birth due to environmental factors.
l 6 9
THE GENETI CS REVOLUTI ON
Other scientists also entered the barnyard to clone animals. In October 2000
they cloned a Holstein cow named Mandy, which eventually won several awards
at an auction ring at the World Dairy Expo in Madison, Wisconsin. Mandy was
described as having strong legs, a broad chest, and a large udder, as well as being a
milk producer at nearly twice the rate of the average cow. Her unborn clone fetched
$82,000 at the auction.
Recently, scientists in Italy reported that they created the world' s first cloned
horse. The horse is in excellent health. This raises the possibility of the next
Seabiscuit or a carbon copy of Kentucky Derby champion Smarty Jones. Texas
A&M veterinarians have also cloned a horse.
Scientists at the Laboratory of Reproductive Technology in the nort hern
Italian city of Cremona reported that they have created their second cloned horse,
produced from the DNA of a gelded thoroughbred Arabian race champion. The
foal, named Pieraz-Cryozootech-Stallion, born on February 25, 2005, weighed
ninety-three pounds and was "in excellent health." The young stallion was
cloned from Pieraz, retired to a stable in the United States after winning en-
durance championships in 1994 and 1996. The birth preserves the lines of a
world-class race horse. Italian scientists used DNA from skin cells obtained from
the former champion, employing the same technique as that used to clone the
sheep Dolly.
Cloning Pets
Cloning was soon moved from the barnyard to the living room. On December
22, 2001, CC (Copy Cat) was bornthe first household pet cloned. CC was a cal-
ico domestic shorthair cloned from a cat named Rainbow by Dr. Mark West-
husin at Texas A&M' s Veterinary Medicine School at College Station, Texas.
CC' s creation was funded by Genetic Savings and Clone, a company that made
its money from people who wanted to duplicate their favorite pets.
Rainbow was a typical calico with splotches of gold, tan, and brown on
white, whereas CC, her clone, had a striped gray coat over white. CC differed
from its genetic donor in its color pattern because color pattern is not strictly
determined by the lineup of genes. Prior to cloning, geneticists explained to the
owners that CC would not necessarily bond with them. CC and Rainbow
were different in other aspects, as well. Rainbow was moderately reserved by na-
ture, whereas CC was playful and curious. Rainbow was chunky; CC was sleek.
Although DNA test results showed that CC was indeed a clone, CC was not an
exact copy, proving that cloning does not lead to exact duplication.
In another case, a couple requested that scientists clone their eleven-year-old
dog, Missy. Willing to pay over $2.3 million to have another dog just like Missy,
the couple requested that Texas A&LM University veterinarians clone Missy. At
the time, veterinarians explained to the couple that cloning a dog was a complex
procedure when compared to other animals because the reproductive system of a
dog is rather complicated. Previously, proponents of dog cloning had claimed
that it would be a definite benefit to society, particularly the cloning of excep-
tional guide, rescue, or search dogs.
1 7 D
REPRODUCTIVE CLONING
In late December 2004 the first cloned-to-order pet sold in the United States
was delivered to a Texas woman. The kitten, "Little Nicky," cost its owner $50,000
and was created from DNA from her cat who had died the previous year. The
company was Sausalito-based Genetic Savings and Clone. The cloning has fueled
a fierce ethics debate.
In August 2005 South Korean scientists, led by Hwang Woo-Suk, successfully
cloned Snuppy, a male Afghan dog.
Cloning Endangered Species
Scientists also considered cloning endangered species to increase their popula-
tions. On October 17, 1999, a team of Russian, French, and Dutch paleontolo-
gists successfully airlifted a twenty-three-ton male wooly mammot h from its
grave in Siberia. The mammot h had been frozen for more than 20,000 years and
was almost complete except for its head, which had been exposed to air. At the
time, scientists proposed that attempts be made to breed a living mammoth from
the DNA taken from the mammot h' s tissues or bones, or sperm or cell nuclei
retrieved from the carcass. Unfortunately, thawing out the animal tended to de-
stroy the cell nuclei, making cloning nearly impossible.
In August 2005, it was announced in New Orleans that two previously cloned
tabby wildcats had naturally mated. This is the first time that clones of two wild
species, or any cats, have done so. Ditteaux, clone of the male African wildcat
Jazz, fathered eight kittens on two clones of Nancy, a female unrelated to Jazz.
The five kittens born July 26 to Madge and three born August 2 to Caty will be
moved to the Audubon Center for Research of Endangered Species.
Transgenic Animals
Human beings use animals for various purposes. For example, we kill animals for
food, and this seems to justify many other uses. But when we clone animals, par-
ticularly warm and furry pets, it prompts most of us to ask questions about the
way we are using animals.
Transgenic animals offer a decided advantage for animal cloning because it
allows an unlimited number of cells to be frozen for a long period of time if
needed, then thawed without loss of unique, favorable traits for future use, if
desired. Ot her advantages include sheep that produce milk with beneficial pro-
teins for patients with diseases such as cystic fibrosis, and cloned livestock that
produce biological proteins that could help people who have diabetes or Parkin-
son' s.
On April 20, 1999, Japanese researchers at the Snow Band Dairy in Hokkaido,
Japan used a mammary cell extracted from colostrum (the milk produced by a
cow shortly after giving birth) to clone twin calves. A week later, on April 27,
Nexia Biotechnologies Inc. of Montreal, Quebec, announced that they had
cloned the world' s first triplet goats named Arnold, Danny, and Clint. Nexia's
goal was to produce transgenic goats with a human gene that would produce milk
l 71
THE GENETI CS REVOLUTI ON
containing spider-silk proteins to be used for artificial tendons and ligaments, tis-
sue repair, wound healing, and sutures.
The world' s first cloned pigs were born on March 5, 2000, for the purpose of
organ transplants. Scientists worked to remove the gene that produces the alpha -
1,3 galactose sugar in pigs which causes an extreme rejection of animal tissues by
the human immune system. The cloning of piglets lacking the gene is important
because of the prospect of providing humans with an endless supply of compati-
ble organs for transplantation. Because of a severe shortage of human organs,
many people worldwide die while waiting for transplants.
In late August 2002, PPL Therapeutics PLC, the Scottish company that
helped clone Dolly, announced that four healthy piglets were born July 25 at the
company' s U.S. subsidiary in Blacksburg, Virginia. A fifth piglet died shortly af-
ter birth of unknown causes. Such piglets are of great medical value because they
have corresponding human organs. But they are also considered of value because
they are not susceptible to mad cow disease and related afflictions that can be
passed on to humans.
When it was first suggested, there was a major concern in transplanting pig tis-
sues into humans. Scientists feared that human cells could be infected with porcine
endogenous retroviruses (PERVs) that exist in all pig cells. In culture, pig pancreatic
islets produce viruses that infect human body cells, but not blood cells. This was
bad news for diabetes researchers who had thought that the pig pancreatic islet cells
and pig cells were a possible alternative in a treatment for insulin-dependent dia-
betes mellitus. Because of this problem, the race to develop pigs for animal-to-
human transplants, which are known as xenotransplants, has been slowed.
However, cloning has a great potential benefit for the livestock industry be-
cause scientists can genetically alter bovine adult cells easily. Scientists clone only
the cells that are transformed. Harvesting and growing adult cells is preferable
when compared to embryos and enables manufacturers to produce quality bio-
logical products such as proteins for humans.
ABS Global, Inc., a small company specializing in reproductive services in
DeForest, Wisconsin, reported that a black bull calf named Gene was the result
of cloning a relatively undifferentiated (unspecialized) stem cell from a thirty-day-
old calf fetus. This was a different process from Dolly' s where they had to reset
genes. Cloned cattle such as Gene are useful because they can be genetically ma-
nipulated to produce drugs or other valuable substances in their milk. Genetic
engineering has been credited as the key precursor to cloning: "Whatever one' s
own personal views about using animals as vehicles for human drug production
or as a source for replenishing defunct human organs, it is important to realize
that it is mammalian transgenesis and not cloning that has opened the door for
such practices. Cloning would have little future, and certainly be of little com-
mercial value, without genetic engineering."
22
Safety of Transgenic Animals
Advanced Cell Technology (ACT) of Worcester, Massachusetts, and Infingen Inc.
of DeForest, Wisconsin, have released data on cloned cattle showing that milk
1 7 2
REPRODUCTI VE CLONI NG
taken from cloned cows is identical to normal cow's milk and is safe for human
consumption.
Animal husbandry has produced gene-altered domestic animals for cen-
turies, suggesting that genetically engineered animals should be regulated like
other farm animals. However, Consumer Reports magazine warned that not enough
is known about the health effects of genetically engineered foods and has called
for labeling of all genetically engineered or cloned fish, poultry, and meat for con-
sumers.
To assure safety of transgenic animals, the Food and Drug Administration
asked the National Research Council (NRC), chartered by Congress, to define
science-based risks to human health involving gene-altered or transgenic animals.
This concerns two types of genetically-engineered animals. First are the bioreactors,
which are animals prized for proteins in their milk or other products useful in
agriculture, such as semen from a cloned prize bull such as Gene. Second are food
sources such as pigs nursed by a sow that is bred with a gene that lets it make
more milk.
Thinking Ahead
Reproductive cloning and gene therapy are already becoming an important part
of our society. However, there is a pronounced fear that it will progress to human
cloning, most likely because the technology has progressed so far and so rapidly.
Wilmut and Campbell' s cloning of Dolly raised three important questions about
the prospect of human cloning:
23
Is it possible to undertake the same operations on human cells?
Will cloners be able to reduce the high rate of failure?
What is the relation between a clone obtained through nuclear transplantation
and animals, born in the usual way, from which the clone is derived?
When we consider reproductive cloning, we are reminded of the same primi-
tive thoughts of those who first opposed in vitro fertilization, genetic engineering,
organ transplantation, open-heart surgery, and other significant breakthroughs:
Indeed many medical developments have been at least temporarily
halted because of ethical qualms. Religious leaders found vaccines ob-
jectional because they interfered with God' s plan for those who should
get sick, and in vitro fertilization was condemned in the 1970s by many
of the same conservative ethicists who today oppose therapeutic cloning.
Organ transplants were once seen as objectionable. And recombinant
DNA technologythe ability to create synthetic geneswas banned
from top universities like Harvard and MIT for years, for fear that hor-
rible and dangerous creatures would be produced. But much of the op-
position melted when the technology was used to create a synthetic
form of insulin to treat diabetics, and today recombinant DNA is used
in virtually every research laboratory in the world.
24
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1 1
CLONI NG A HUMAN
Mary had a little lamb, whose fleece was slightly gray,
Didn' t have a father, just borrowed some DNA.
Sort of had a mother though the ovum was on loan,
Was not so much a lamb kin as a little lamby clone.
Soon it had a fellow clone and soon there were some more,
They followed her to school one day, all cramming through the door.
It made the children laugh and sing and thrilled them to the soul.
But there were just too many lambs for Mary to control.
No one else could herd the sheep, their imprints didn' t vary,
The cloners sought to fix it up by simply cloning Mary.
So clone they did and Newsweek said it was extraordinary,
But now they don' t know what to do with Mary, Mary, Mary . . .
author unknown
Cloning has always caught the public imagination. Throughout the twentieth cen-
tury and now into the early twenty-first century, newspapers and various reports,
books, movies, television, and conversation have focused on the implications of
cloning humans. The possibility of cloning a human has resulted in a media
frenzy with thoughts of a Utopian society much like Aldous Huxley's Brave New
World. As a result, many fear that Huxley's fiction of yesterday might become to-
day's reality. Mary Midgely, widely respected senior lecturer in philosophy at
Newcastle University in England, once asked why anyone would want to clone
humans even if they could. She advised readers to forget fears like those raised in
Brave New World and suggested instead they concentrate on real-life research.
THE GENETI CS REVOLUTI ON
For many the mere mention of human cloning tends to inspire paranoid vi-
sions of many Hitler clones. In the political-science fiction book and film, The
Boys from Brazil, two clones of Hitler were purportedly produced from a cell con-
taining Hitler' s DNA. The cell was in turned joined with an egg, and an embryo
was formed that contained solely the genes of Hitler, with only the necessary
ones coming from the woman.
1
The science fiction-like experiment in The Boys from Brazil was done for
many reasons. One of the reasons was to bring the world under Nazi domination,
but the experiment was primarily intended to test the clones' behavior away from
one another and to see if any particular kind of attitude could be passed on from
one clone to another. Results showed that the cloned boys had Hitler' s genes and
both displayed Hitler' s violent psychotic personality, despite being raised apart
and with totally different lifestyles.
In 1978 science writer David Rorvik wrote in the book In His Image that in
1973 a millionaire asked to have himself cloned. After two years of experimenta-
tion, the procedure was carried out in secret. A single cell was taken from the mil-
lionaire's body and fused with an egg that had its nucleus and DNA removed.
The resulting embryo was implanted into a surrogate woman' s womb and a baby
was born. The alleged cloning was said to have occurred somewhere in the Ori-
ent, in an unnamed laboratory, by unnamed scientists. In addition, the child was
unnamed, as were his mother and father.
2
No corroborating evidence could be shown to prove Rorvik' s story. Not even
Lippincott, the publisher of the book, supported Rorvik' s story, and the case re-
sulted in a $7 million lawsuit. In his ruling, the judge of U.S. District Court in
Philadelphia ruled that Rorvik' s book was a work of fiction and that the cloning
experiment described in the book never took place. Rorvik did not contest the
ruling.
The Good and Bad of Human Cloning
There are pros and cons to every issue and human cloning is no exception. Be-
cause ethical implications of human cloning balance on a fine line, there is cur-
rently a heated debate over the potential cloning of a human. Many who have
followed the human cloning debate believe that the real argument is about poli-
tics, not science. Yet, the primary debate over human cloning is fundamentally
and undeniably about life. Beyond a shadow of doubt, certain aspects of human
cloning already have become a part of our current society.
Initial reactions of ethicists to human cloning were that it was uncon-
scionable, even though in many countries it is not explicitly illegal. Some believe
that human cloning is unnatural; however, unnatural does not necessarily mean
bad. Others fear that human cloning has progressed so quickly that it is not so-
phisticated enough.
In human fertility cloning the male donates a body (somatic) cell and the fe-
male donates an egg cell (ovum) from which the DNA has been removed (enucle-
ated egg). The DNA from the male's body cell is implanted into the female's
enucleated egg cell. In so doing, the majority of the genetic material is obtained
1 7 6
CLONI NG A HUMA N
from the male but a minute amount of DNA is left in the enucleated egg. As a re-
sult, the resulting child is potentially a partial genetic mix.
Numerous reasons are given by proponents for cloning a human, but one of
the most obvious and understandable reasons is replacing a dead or dying child.
Consider the following hypothetical case:
Conception had been difficult for Jim and Ann Thomas, both thirty-
two, but eventually Ann gave birth to their son Brad. He was the center
of their lives. Then, one day, while watching an outdoor baseball game,
Brad was struck by lightning and died. Understandably, Jim and Ann
were devastated. Searching for a glimmer of hope, they asked scientists
to take a cell from Brad's body, clone it, and implant the clone in Ann' s
uterus so that she might be able to give birth to Brad II. The procedure
was successful and Brad II became the center of the Thomas family,
bringing much happiness.
Although the story has a happy ending it raises the following questions:
Was it moral to allow Ann to bear a cloned replacement for Brad?
Should grieving parents like Jim and Ann be denied the opportunity to clone
an identical copy of Brad?
Consider another case:
In April 1991 Bob and Mary Smith of St. Paul, Minnesota, began liv-
ing through every parent' s nightmare. Susan, their fifteen-year-old
daughter, was diagnosed with acute lymphoblastic leukemia, a fatal
blood disease. Sadly, Susan died within a few months of the horren-
dous diagnosis. Both Bob and Mary were devastated and decided to
ask that Susan be cloned. The cloning was successful and the twin-
clone, Susan II, became a part of the elated Smith family.
The Smiths' story, like that of the Thomas' s story, had a happy ending, yet other
questions surfaced:
Is it right for a couple to use one child to clone another?
Can someone brought into the world for such a well-defined purpose ever feel
that she is loved for who she is?
Should the Smith and Thomas families have been allowed to exercise the
cloning option?
No doubt, cloning from an already existing child is controversial any way it is
looked at. Opponents of human cloning, understandably sympathetic to the
Thomas and Smith families' losses, question whether or not this is an appropriate
way to deal with human loss. They argue that human cloning to replace a dying
or dead child is unreasonable, not only from an ethical and moral standpoint,
1 7 7
THE GENETI CS REVOLUTI ON
but also because there are currently so many children worldwide who need
adoption.
Unlike the process of cloning embryos, cloning from an already existing hu-
man allows the parents or the individual donor to know exactly what the twin-
clone will look like ahead of time. In the case of both Brad II and Susan II,
cloning produced exact physical replicas of the dead children. Understandably,
personality and other factors cannot be replicated because environment plays a
huge role in shaping a person' s identity, even before humans are born.
Another justification given by proponents of human cloning is to provide a
child to a couple who cannot produce a child naturally because of infertility. Hu-
man cloning is considered by many scientists to be superior to in vitro fertiliza-
tion for treating infertility because any health problems in the child can be
eliminated from the beginning, ensuring a couple a healthy child. Opponent s of
human cloning believe that allowing even limited human cloning could result in a
national black market for women' s eggs. This could result in unethical (rogue) sci-
entists producing cloned infants. Opponent s say that it is as if the "birds and the
bees" have been rendered irrelevant.
A third major reason for cloning humans is vanity. The following question is
frequently asked: Will humans someday be genetically engineered and cloned ex-
clusively for vanity reasons? The answer, for many, is "yes" because society will
do all kinds of things for money. In vanity cloning, it would be possible to clone
someone famous, a departed loved one, a spouse, or even oneself, providing the
person with exceptional talents he or she did not possess while living. This might
include creating persons with small body size and weight for space flight or to be
winning jockeys, or those cloned for their musical talents or athletic abilities.
Even though cloning is a costly form of technology, it is likely that wealthy
people such as movie stars and athletes would be willing to pay high prices for a
clone of themselves or someone dear to them. Today, even middle-income cou-
ples spend a great deal of money on in vitro fertilization, and it is likely they
would be willing to pay as much or more to clone their children, grandchildren,
pets, or others close to them. Proponents of vanity cloning argue that if living
persons want to clone themselves or others dear to them and can afford to be
cloned, it should not be prohibited or considered a crime.
Proponents of human cloning argue that there would be ultimate potential
value to society if exceptional athletes, scientists, and musicians were cloned and
educated in the twenty-first century. The prospect of cloning superstar basketball
players Michael Jordan and Shaquille O'Neal or tennis stars Venus and Serena
Williams; or replicating the great scientist, Albert Einstein, seem real. Or imagine
cloning past political leaders like Abraham Lincoln, John F. Kennedy, Winston
Churchill, or Franklin and Teddy Roosevelt, or reproducing the physical beauty of
Elizabeth Taylor or Julia Roberts. Certainly no one will dispute the fact that leader-
ship and good looks are assets to not only an individual, but to society in general.
No one will argue that these and other clonings would add greatly to society's
cultural value, making life more valuable for their twin-clones. Although physi-
cally like the cloned individual in beauty, height, and build, it is highly unlikely
that the cloned twin would have the same personality, soul, spirit, behavior,
thoughts, or any other characteristics as the person he or she was cloned from. It
l 7 B
CLONI NG A HUMA N
is a well-known fact that identical twins conceived in the natural way and raised
under the same roof by the same parents t urn out to be quite different because
their personalities and identities are shaped by environment. Just as identical
twins conceived in the natural way live separate lives and have separate souls,
clone-twins would as well.
Erik Parens, a bioethicist at the Hastings Center in Briarcliff Manor, New York,
believes proponents and opponents of human cloning share the same mistaken
idea that you can clone a "self." "But as everyone knows, you can't clone a self be-
cause a self is a function of infinitely more than one's own genetic material."
3
Another reason given for cloning humans is more efficient communication.
Society would benefit both culturally and financially from human cloning because
it has the potential to create more efficient communication among people. Clones
who are alike in traits, including beauty, great genius, etc., would improve the
species, making life more pleasant by having a better understanding of each other.
Proponents also list as a definite advantage to human cloning the ability of
clones to serve as "human banks" to provide spare parts for organ transplants.
This would include production of embryonic replicas of a person, to be frozen
until needed as a source of organs for transplantation to their genetically identi-
cal twin. After obtaining a person' s DNA, scientists would insert it into cells,
grow the desired new limbs, organs, skin, and so on, and then transplant the tis-
sue back into the same person. The procedure would allow clones to be gene-
tically engineered with special immune system genes that would allow organs to
be transplanted without rejection.
In 1997 Dr. Patrick Dixon, author of The Qenetic Revolution and an authority
on the ethics of human cloning, predicted that sometime in the future headless
human clones would be used to grow organs and tissues for transplant surgery.
He made the prediction after it was reported that British scientists had created a
frog embryo without a head. Dixon believes that the technique used to create the
headless frog might be modified to grow human organs such as liver, hearts, pan-
creases, and kidneys in an embryonic sac living in an artificial womb.
4
According to Dixon: "I believe that there will be great pressure to combine
technology with the creation of partial fetuses, missing heads, arms or legs, as or-
gan factories for tomorrow' s people. These will be developed on an experimental
level somewhere in the world in countries where there is little or no gene legisla-
tion within the next 5-10 years because of overwhelming demand. International
inconsistencies on various aspects of genetic engineering, including human
cloning, urgently need to be ironed out."
5
Later, speaking on BBC World Service,
Dixon commented:
We will see the creation of human beings which are growing, yet tech-
nically dead, because they have no brain-but is that the kind of world
we want to live in? Hundreds of these humanoids could be made.
Their creation will raise profound questions. The real issue is not
Dolly the cloned sheep, or now the headless frog. It is how we want so-
ciety to use gene technology now that we have the ability to do more
or less whatever we like with life, designing all kinds of bizarre crea-
tures or hybrids. I am far more concerned by tomorrow' s headlines
1 7 9
THE GENETI CS REVOLUTI ON
than today's, and by the fact that most people are years behind reality
when it comes to thinking through the impact of what is going to hap-
pen next.
6
Growing select human organs became a reality in the laboratory when scien-
tists at Advanced Cell Technology (ACT) in Worcester, Massachusetts, reported
that they had used cells derived from cloned cow embryos to grow kidney-like or-
gans that functioned and were not rejected when implanted into adult cows. Sci-
entists took a single skin cell from a cow's ear and fused it with a cow's enucleated
egg to make a cow embryo. Stem cells were removed from the embryo, pro-
grammed to develop into kidney cells, and allowed to mature until they functioned
like a miniature kidney. Scientists then implanted several of the mini-kidneys under
the skin of the cow that had donated the ear cell.
The mini-kidneys produced urine that drained into attached synthetic bags
(bladders) for several months. Whet her the mini-kidneys performed all of the
jobs performed by normal human kidneys is not known. The ACT research was
the first to show that cells taken from a newly created clone could be made to
grow personalized, genetically matched organs, working together as a functioning
organ, and coexisting with the body' s immune system.
7
Opponent s of human cloning remind us, however, that just as it is possible to
clone the good and desirable, the same technology can be used to clone the evil.
Imagine how appealing cloning would be to a dictator or terrorist like Osama bin
Laden or Saddam Hussein, who would revel in watching numerous copies of
themselves grow up to populate the world with what they perceived as a new race
of genetically superior people. Human clones could result in cloned armies of
people to work assembly lines; to supply large military troops for war such as
those bred for war by the evil Saruman in The Lord of the Rings; or to run the
world. Such clone wars would result in a lack of morality or immorality since
killing or being killed would have no great meaning.
Opponents of human cloning also remind society of the ramifications of
flaws and failed experiments. Fritz Lang's 1926 science-fiction classic Metropolis,
the first film to portray an artificially constructed evil twin-clone, depicts the
story of cloning gone awry. In the story, clones turn out to be different from their
originals in some pivotal, often destructive way; and the cloners usually overesti-
mate their power to control the clones.
8
Today's opponents of human cloning worry about failed experiments as in
Lang's Metropolis, saying that human cloning technology has not yet been per-
fected and could lead to death or malformation of the fetus. Opponent s cite
many animal cloning experiments that have produced high failure rates resulting
in birth defects, multiple miscarriages, or mental and emotional problems.
Opponents cite very low success rates of only about 1 percent of attempted
clones in animals that result in a successful pregnancy. This is despite years of at-
tempts after the cloning of Dolly, with a considerable amount of time and re-
search money put into it. Opponents of human cloning remind us that it took
Wilmut and Campbell 434 oocytes to produce Dolly. This raises a startling ques-
tion: Suppose the survival rate for appendectomies was one in 434; would sur-
geons be anxious to operate?
1 BD
CLONI NG A HUMA N
Admittedly, with such a potentially low survival rate it would be a game of ge-
netic roulette. Cloning a baby would require hundreds of egg cellsmore than a
woman is physically capable of donatingand in nearly 100 percent of the cases
cloning would give rise to abnormal embryos and fetuses, almost all of which
would abort. Based on statistics, at least one abnormal child would be born.
9
Other problems would likely surface even if scientists were able to induce
complete nuclear programming 100 percent of the time. This is because abnor-
mal adult donor cells during their lifetimes are exposed to a number of stressors
including carcinogens, radiation, and chemical mutagens. If cells were grown in
culture (in vitro), quite likely there would be additional mutations, making it im-
possible to select normal donor cells.
However, proponents of human cloning argue that it is ridiculous to ban hu-
man cloning just because the procedure is considered by some to be not perfectly
safe. They are quick to remind opponents that there is no area of human activity
free of accidental death and that human cloning is no exception. Citing statistics
that reveal thousands of persons die each year in automobile, motorcycle, and
plane accidents, proponents remind us that society would never think of banning
automobiles, motorcycles, or airplanes.
Proponents believe that the possibility of a cloned child with abnormalities
would not be any different from the possibility of having a child with abnormali-
ties born by in vitro fertilization. Like in vitro fertilization in the past, propo-
nents believe that cloning procedures will be perfected to the point where the risk
of miscarriage or death to the baby will be the same as for any birth.
Another reason given by opponents not to clone humans is that cloning
would cause males to be reproductively obsolete because cloning requires only
oocytes, any somatic cell, and a woman' s uterus to develop in. They believe that
it would allow control of the sex of future children since the sex of the cloned
offspring is the same as that of the adult from whom the donor nucleus is taken.
10
One of human cloning opponents' greatest fears is that cloning technology
might be used irresponsibly to create large sets of genetically identical copies of
humans, resulting in loss of diversity and human uniqueness. It is not for society
to end evolution; diversity is our best hope. The uniqueness of each individual,
and the consequent variability among individuals in biological populations of
sexually reproducing organisms, provides the sine qua non for evolution by Dar-
win' s mechanisms of natural selection.
11
Worldwide, there would be thousands of people identical to you, different
from each other only by names and perhaps dress. Walking down the street as one
clone among hundreds would be a disaster. This would have drastic long-term ef-
fects on society's self-perception and would overall cause the ratio of sexes to fluc-
tuate wildlytoo many men or too many women. Natural selection works only if
individuals of a population are distinctively different, one from the other.
Darwin' s theories require that variability be conferred by genetic distinctive-
ness. Darwin' s process works by selective elimination and preservationby im-
parting higher reproductive success to a subset of individuals fortuitously better
adapted to changing local environments. By reproductive process, a lineage con-
tinues by making more members; sex provides variability among individuals by
mixing the DNA of the male and female parents in each of the offspring.
12
l B l
THE GENETI CS REVOLUTI ON
Scientists remind us that if everyone has the same DNA somewhere in the fu-
ture we would lose the ability to clone because it would be necessary to resort to
natural reproduction, causing a considerable amount of inbreeding. This would
cause many problems: for example, occurrence of diseases that could wipe out an
entire population. However, others argue that unlike in vitro fertilization, cloning
would allow replication of the healthy to bypass the risk of genetic disease con-
tained in the lottery of sexual recombination.
With regard to human cloning, Stephen Jay Gould posed the following ques-
tions:
13
Are clones distinct individuals?
Does each member of a clone have a soul?
Am I still a distinct individual if I clone a daughter from a cell scraped from the
inner lining of my cheek?
Gould believes that such fears about human cloning are misplaced because
the above questions have clear answers. Because identical twins share mitochon-
drial as well as nuclear DNA, gestate in the same womb, and usually grow up in
the same environment, they are much closer than twin-clones. They become dis-
tinct individuals because of environmental influences.
Gould further believes that human cloning should be studied and debated
with enthusiasm and interest. "We can spell out unacceptable scenarios for hu-
man cloning, and we should pursue our ethical debate on this subject with rigor
and vigilance."
14
George Will, syndicated columnist, recently wrote: "There are some things hu-
manity cannot get used to without jeopardizing its humannesswithout becoming
beastly. Creeping toward us, as on little cat feetlittle monkey feet, actuallyis
perhaps the gravest imaginable crisis, one that could result in the end of history
as a distinctively human, and humane, story."
15
Will was referring to ANDI, the
first genetically-modified primate created. ANDI was a baby rhesus monkey with
jellyfish DNA that glows green in the dark. The Oregon Health Science Univer-
sity researchers who created ANDI said their goal was not to tinker with the hu-
man blueprint but to use monkeys such as ANDI to advance medical research
and wipe out diseases. Rhesus monkeys such as ANDI share 95 percent of their
genes with humans. According to Will, "ANDI was created, not begotten; the re-
sult of manufacture, not procreation. Humans are primates, which makes us (hu-
mans) next in line for genetic ' enhancement.' "
16
The Eugenics Connection
Whenever human cloning is discussed, invariably the topic of "eugenics" comes
up. The idea of eugenics (improving the race through breeding) can be traced
back to Plato's Republic or even before. In Mendel' s time, eugenics was a primary
objective of experimentation, and after publication of Darwin's Origin of the
Species in 1859, there was renewed interest in the study and application of eugenics.
1 8 2
CLONI NG A HUM A N
However, interest in eugenics probably originated with Francis Galton, a first
cousin of Charles Darwin, who coined the word eugenics (meaning "good genes").
To many, the term "eugenics" invokes a sense of horror, mainly because the his-
torical record of eugenics is not encouraging. In Germany and other countries, in-
terest in eugenics flourished after the turn of the twentieth century. There was fairly
widespread interest in the theory of eugenics, which advocated that the human race
could be improved if "genetic purity" or ethnic cleansing was encouraged.
The horrors of Nazi Germany represent the most extreme case of eugenics.
Hitler' s goal was to improve the human gene pool by large-scale elimination of
select groups of people in his attempts to raise a perfect "master race." Hitler' s
extermination policies began with the large-scale elimination of people with dis-
abilities; however, the darkest period for eugenics occurred when Nazis embarked
on a "final solution" to the Jewish "problem": the Holocaust. The smell of
Auschwitz remains with us today. Nazi Germany justified its horrendous actions
by saying that it demanded the sacrifice of the minority to advance the interests
of the majority. Syndicated columnist Cal Thomas, wrote: "We need to return to
a uniform life ethic covering the unborn, the handicapped, the elderly, racial and
religious minorities, in short, all human life. We still recoil at what Hitler did to
the Jews, gypsies, homosexuals, and the sick."
17
Ethnic cleansing continues today in various parts of the world. Opponents of
human cloning believe that the technology has the potential to become a major
part of ethnic cleansing. However, supporters of human cloning argue that it of-
fers the chance of a new life for those whose lives ended prematurely or unjustly.
They believe that eugenics offers the potential for partial restitution of great in-
equities of the past. For the first time, they say, eugenic cloning would offer Jew-
ish people a time to reconstruct, as millions of victims of the Holocaust could be
cloned to recover lost genetic strains. In Russia, human cloning could have the
potential to replenish the gene pool that was diminished by Stalin's mass execu-
tions of millions, many of whom were Russia's most skilled and brightest.
Today, gene technology has made it possible to isolate, splice, insert, re-
arrange, recombine, and mass produce genes and to bypass natural selection. Sci-
entists are able to insert any gene, or gene combination, into the human genome.
This includes genes for skin color, muscle development, mathematical or scien-
tific abilities, musical skills, or intelligence. Such genetic enhancement has made it
potentially possible to improve the appearance or abilities of individuals and has
allowed scientists to remove individual genes from one individual and introduce
them into another, even of another species.
To many, fabricated (designed) individuals are seen as a step down the road to
Huxley's Brave New World and the production of cadres of "gammas" and
"deltas" where parents can selectively abort their unborn children until they ob-
tain a child with a genetic profile characterized by high intelligence, exceptional
sports or musical skills, or other desired characteristics.
Such genetic manipulation raises serious moral and ethical concerns, particu-
larly for indigenous groups who believe that any violation of the natural order is
abhorrently wrong. To breed blue-eyed blonde babies, much like radishes grown
and nourished in the family garden, or to genetically boost the skills and physical
strength of a dictator' s army are potential consequences of human cloning.
1 B3
THE GENETI CS REVOLUTI ON
Currently, a company called Clonaid, run by the religious sect Raelians and
headed by Dr. Brigitte Boisselier, advertises its selection of human embryos, each
guaranteed free of all genetic defects. Described in detail in the advertisement are
the gender, IQ, eye color, and other traits of each embryo, a prime example of
contemporary aggressive eugenics.
Kevin Fitzgerald believes that such control is a prime example of the loss of
freedom. "When we attempt to control all the various elements of our lives to
the extent that this technology seems to indicate, we have in a sense chosen to re-
linquish some of that freedom (whether we are successful or not). We can no
longer now be the creatures we were before."
18
President Clinton's 1995 National Bioethics Commission
Responding to what he termed the "troubling prospect" of cloning human be-
ings, President Clinton convened the National Bioethics Advisory Commission
(a panel of experts in medicine, science, law, ethics, and theology) to review the
ethics and legality of human cloning and the ramifications cloning would have for
humans. Created in October 1995 by President Clinton' s executive order, the
eighteen members of the commission were appointed for terms ranging from two
to four years. Harold T Shapiro, economist and president of Princeton Univer-
sity, served as the commission chair.
President Clinton asked the commission to provide general and contextual
advice on human cloning. He also requested that the commission make recom-
mendations to the National Science and Technology Council and other govern-
ment entities regarding bioethical issues arising from human biological and
behavioral research, as well as the clinical applications of such research. The pres-
ident asked the commission to report back to him in ninety days on the implica-
tions of human cloning on what he called "the sacred family bond at the very
core of our ideals."
The president' s request was hailed by scientific experts as an important first
step toward insuring that reproductive technology be neither diminished or al-
lowed to get out of control in the United States. Opponents of human cloning
were disappointed, saying that President Clinton and the Bioethics Commission
did not go far enough. Soon after, opponents called for a complete ban on human
cloning, which they feared would rob the human race of its individuality. Legali-
ties aside, the prospect of human cloning gave rise to profound ethical questions
for the commission to consider. The foremost question was: What are the psy-
chological impacts of being born as a genetic duplicate of one' s parent?
Hearing from biologists, lobbyists, and ordinary citizens, the commission re-
ported back to the president in ninety days with a three-part recommendation.
First, the current moratorium on human cloning (mandatory for those with fed-
eral grants, voluntary for everyone else) should be extended. Second, a federal
law should ban human cloning outright. Third, a "sunset clause" should limit the
life of any anti-cloning law.
19
As a result of the commission's recommendations, as well as the news that re-
searchers at the Oregon Health Science University had cloned two rhesus monkeys
l 8 4
CLONI NG A HUM A N
from embryos, President Clinton decided to restrict the use of federal funds for
human cloning. Defending the experiment, Oregon researchers said they created
the monkey clones to make cloning research more efficient and economical and
had no intent to clone humans.
Prior Regulatory Commissions
The Clinton Commission was not the first set up to regulate ethical and moral is-
sues. The first National Bioethics Commission was created in 1974 to address re-
search on human fetuses and issued its report by its expiration date of 1978. The
1974 commission created widely respected reports on the protection of human
research subjects, including prisoners and children; those recommendations also
became law. The first federal ethics board, created by Congress in 1985, quickly
turned into a battlefield over abortion issues. The board expired in 1989 without
issuing a single report.
In 1994, a National Institutes of Health panel concluded that certain types of
human embryo research were not justified, whereas other types were ethically ac-
ceptable. Among the accepted types of research were those embryo research proj-
ects that would provide insights into genetic diseases.
President Clinton's Cloning Prohibition Act of 1997
President Clinton' s Cloning Prohibition Act of 1997, modeled on the recommen-
dation of the National Bioethics Advisory Commission, outlawed any somatic
cell nuclear transfer intended to create a human being. However, it also included
a five-year sunset clause and was careful not to restrict other important and
promising workthe right to clone molecules, DNA, cells, tissues, or animals.
20
In considering the Act, President Clinton recognized the great potential for
advances in medicine and agriculture when he decided not to recommend that
cloning animals and human genes be outlawed. Realizing that human cloning had
the potential to be used for evil purposes, the president felt that other forms of
cloning held potential to do great things for humanity. The dilemma, Clinton said,
was resolving the desire to use cloning as a means for curing diseases, which the
president said was possible "without raising the kind of ethical implications that,
in effect, we're in the business where people are trying to play God."
21
President
Clinton compared human cloning to splitting of the atom during the nuclear age
and recommended that scientists move with caution and care: "Each human life is
unique, born of a miracle that reaches beyond laboratory science. I believe we
must respect this profound gift and resist the temptation to replicate ourselves."
22
Some religious groups warned that human cloning was disrespectful and un-
natural and that scientists and others who supported it were playing God. Warn-
ing against trying to play God, President Clinton imposed a ban on federal funds
for human cloning experiments, saying, "Any discovery that touches upon hu-
man creation is not simply a matter of scientific inquiry. It is a matter of morality
and spirituality, as well."
23
1 B5
THE GENETI CS REVOLUTI ON
The accusation of "playing God" has been a vague but recurring criticism
every time there is a major advance in biomedicine and was used when advances
in birth control pills, in vitro fertilization, and heart transplants occurred. There-
fore it was not surprising that the accusation was made when scientists advocated
human cloning.
President Clinton asked for a voluntary moratorium on human cloning ex-
periments in the United States until legal and ethical issues could be sorted out.
The President declared that only a voluntary moratorium would ensure that ethi-
cal issues were fully debated. He excluded from his directive any privately funded
research.
Marie Di Berardino, distinguished Professor Emerita at Allegheny Univer-
sity of the Health Sciences in Philadelphia, supported a ban on human cloning,
saying, "There are these characters around who are going to go ahead with human
cloning despite the strong public sentiment against it. We have to permit legisla-
tion. A ban on human cloning would not hamper basic research. That' s a red flag
that very liberal scientists are holding up."
24
Taking a firm stand against human
cloning, Di Berardino emphatically stated that cloning research should proceed
with other animals, but not with human material.
National and International Concerns
The concern as to whether human cloning should be allowed really began in 1993
at George Washington University Medical Center in Washington, D.C. Dr. Jerry
Hall and colleagues experimented with human cloning and in doing so opened a
Pandora' s box of moral and ethical questions.
Hall and his team first announced they had created sixteen human embryos
in a laboratory dish and separated them into forty-eight individual cells. In the ex-
periment, two of the separated cells survived a few days and developed into new
embryos of thirty-two cells each. However, each embryo was declared defective
and destroyed shortly thereafter.
When Hall's experiment was announced, the public was outraged, with out-
cries coming from both sides of the Atlantic. One German magazine called Hall's
cloning research "unscrupulous." Even proponents of human cloning at the time
admitted that the experiments were premature, but that it was quite likely a pos-
sibility for the future.
The Vatican condemned Hall's experiment, calling it "perverse." Two Ro-
man Catholic doctrinesnatural law and ensoulmentdictated a closed position
on the issue and the Roman Catholic document Instruction on Respect for Human
Life (1987) presented a reasoned plea for society to follow natural methods of hu-
man procreation. The Roman Catholic Church cited human cloning as contrary
to moral law and in opposition to the dignity both of human procreation and
of the conjugal union. Instruction on Respect for Human Life speaks of the embryo as
the unborn child who must be cared for, to the extent possible, in the same way
as any other human being. Ensoulment, the second relevant Catholic doctrine, is
the belief that at conception God imbues each human with an immortal soul.
25
The Jewish faith took a liberal stance on human cloning, encouraging people
l 8 6
CLONI NG A HUMA N
to view God' s act of creation as a transformation process. In a Hastings Center re-
port, Jonathan Cohen wrote that God invites humans to become created co-
creators in His ongoing creation. Given this charge, and in view of widespread
human disease and the promise of biotechnology, Cohen questioned: Would it
not, in fact, be morally wrong to bypass the modern development?
26
Ian Wilmut, who cloned Dolly, expressed his views on human cloning at a
cloning forum organized by the American Association for the Advancement of
Science. Expressing his views, Wilmut used a slide (all in capital letters) to em-
phasize his views on human cloning:
WE SHOULD NOT COPY PEOPLE
BECAUSE WE SHOULD TREAT
EACH CHILD AS AN INDIVIDUAL
AND NOT AS A COPY
OF ANOTHER PERSON
27
Later, Wilmut added, "It would be naive to say that we can completely prevent
this. I don' t find that frightening. I find it sad."
28
Wilmut also pointed out various other benefits of cloning, especially where
pharmaceutical manufacturing, animal husbandry, and organ transplants were
concerned. Xenotransplantation (the use of animal organs in people) was among
Wilmut' s expressed interests: "Cloning will provide, for the first time, an oppor-
tunity for precise genetic modifications to farm animals."
29
In 2005 Wilmut and motor neuron expert Christopher Shaw of the Insti-
tute of Psychiatry in London were given a license by the British government to
clone human embryos for medical research into the cause of motor neuron dis-
ease. The experiments do not involve creating cloned babies. The decision by the
Human Fertilization and Embryology Authority means a step closer to medical
research that has the potential to revolutionize the treatment of motor neuron
disease. The project does not use stem cells to correct the disease, but the cells
will help scientists develop future treatments.
On February 11, 1997, a bill was brought before the U.S. Senate that would
have criminalized human cloning at the federal level. However, protests from the
scientific community about the Republican leadership's haste in bringing the bill
forward killed the bill. Shortly thereafter, on February 23, 1997, Dolly the sheep
was displayed to the media, the first large cloned animal using DNA from an-
other adult. Several months later, in June 1997, messengers to the annual meeting
of the Southern Baptist Convention passed a resolution supporting a U.S. gov-
ernment ban on funding human embryo research and asked that human cloning
be prohibited.
Setting Off a Furor
In December 1997 the nation was dealt a bombshell when Chicago physicist
Richard Seed announced plans to clone a human on National Public Radio' s All
Things Considered. The announcement set off an emotionally charged national
1 B7
THE GENETI CS REVDLUTI DN
debate. As a result of Seed's announcement, President Clinton immediately re-
newed efforts for federal legislation to outlaw both public and private attempts to
clone a human.
When congress reconvened in January 1998, Republican leaders promised
quick action to ban human cloning but not existing human scientific research. A
bill titled The Human Cloning Prohibition Act was sponsored by Christopher S.
Bond (R-Mo.). The bill was stopped by opponents who used a parliamentary pro-
cedure to prevent debate. Although supporters sought to force a debate on the
bill they failed to muster the three-fifths majority required to override the objec-
tions. Forty-two Senators supported consideration of the bill and fifty-four op-
posed it. Under Bond' s bill someone found guilty of using cloning technology
with human cells would face fines and ten years in prison.
30
The major lobbying effort against Bond' s bill was by President Clinton' s ad-
ministration and various scientific groups including the American Cancer Soci-
ety, Association of American Medical Colleges, the Federation of American
Societies for Experimental Biology, American Council for Cell Biology, and the
Biotechnology Industry Association. In addition twenty-seven Nobel Prize-
winning scientists also wrote to President Clinton and members of Congress to
oppose the bill.
Other foes of Bond's bill were Senators Dianne Feinstein (D-Calif.) and Edward
Kennedy (D-Mass.) who introduced their own bill. The Kennedy-Feinstein bill
prohibited the placement of cloned human embryos in a uterus (reproductive
cloning), but allowed the use of clones in research (therapeutic cloning). Their bill
included fines but no prison terms for violators and had a life of ten years.
In general, the scientific community favored the Kennedy-Feinstein bill over
the Bond bill. Dr. David Baltimore, Nobel Prize-winning scientist, said that he
believed that someday human cloning would be morally acceptable as a techno-
logical means to aid infertile couples. He recommended that the U.S. govern-
ment follow the 1980s regulation of genetic engineering. Although there was
considerable opposition to genetic engineering at the time it was first proposed,
Baltimore said he believed that it was now an accepted technology of medical
science.
31
Calls went out throughout the world for greater government control of hu-
man cloning experiments. Vatican officials, as well as members of the U.S. Con-
gress, called for a total ban on cloning humans. Pope John Paul II criticized
scientific experiments such as human embryo cloning that threatened the dignity
of human life. In a strong statement, the pope condemned human embryo
cloning and urged physicians to "defend without compromise life and the dignity
of people, operating with respect to moral law. True humanism can never allow
methods and experiments that constitute threats against life."
32
The fifteen-member European Union, which had previously banned human
cloning, asked a scientific committee to consider whether other forms of genetic
manipulation should be regulated. However, Harold Varmus, then head of the
National Institutes of Health (NIH), told lawmakers that cloning a human being
was not consistent with traditional ideas of Darwinian biology concerning hu-
man individuality and diversity. Varmus suggested that interference with the ge-
netic diversity of an entire population would be a disaster.
l BB
CLDNI NG A HUM A N
Varmus further suggested that there were hidden risks in making a person
from a cell that was already many years old because of accumulated mutations.
He suggested that the U.S. government not support human cloning, and he and
others called for a need to legislate the rights and privileges of such clones. Dis-
cussion of human cloning also centered around U.S. laws, as well as laws in other
democratic countries, to control the behavior of rogue dictators in totalitarian
countries.
Meanwhile, the Southern Baptist Convention continued its effort to elimi-
nate human cloning. On June 16, 1999, the Convention passed a resolution re-
peating its request for the U.S. government to continue its ban on federal funding
for human embryo research and asked that privately funded researchers also stop
their research voluntarily.
In early August 2000 the U.S. House of Representatives voted 265-162 to ban
all forms of human cloning with violations punishable by fines of $1 million or
more and up to ten years in prison. The vote to criminalize cloning was backed by
200 Republicans, 63 Democrats, and 2 Independents. However, many scientists,
patients' groups, and the biotechnology industry opposed the ban because it out-
lawed therapeutic cloning for potential disease treatments.
In 2001 the National Academy of Sciences (NAS) panel concluded that hu-
man cloning should be banned because of significant risks. Maxine Singer, presi-
dent of the Carnegie Institution, who chaired the NAS panel, said, "Studies of
the cloning of animals have indicated very real safety concerns both for the clone
and the mother. It seems unwise to proceed to clone a human being."
33
Despite
impassioned opposition, some scientists continued to explore and perform hu-
man embryo cloning.
Eve: The First Human Clone?
On December 26, 2002, an allegedly cloned, healthy seven-pound girl of Ameri-
can nationality and nicknamed "Eve" by scientists was delivered by Caesarean
section at an undisclosed location somewhere outside the United States. The
baby, according to scientists at a company called Clonaid, was an exact genetic
duplicate of its mother, a thirty-one-year-old with an infertile husband. To date,
the cloning of Eve has not been officially confirmed by experts.
Clonaid was founded in the Bahamas in 1997 by Claude Vorilhon, a former
French journalist and leader of a sect called the Raelians. Vorilhon claimed that a
space alien visited him in 1973 and revealed that extraterrestrials had created all
life on earth through genetic engineering. Dr. Brigitte Boisselier, who identified
herself as a Raelian "bishop," said she accepts Vorilhon (known as Rael) as her
spiritual leader. In the past, Vorilhon had claimed to be a race car driver, racing
journalist, and author of Let's Welcome Our Fathers from Space.
Dr. Boisselier, science director at Clonaid, said FDA officials encouraged her
to sign an agreement stating she would not attempt to clone a human in the
United States until the law on such procedures was clarified. Disappointed, Bois-
selier closed her U.S. laboratory, saying, "It' s a pity that cloning could not happen
in the United States because it is the most advanced country for science."
34
1 B9
THE GENETI CS REVDLUTI DN
The Food and Drug Administration (FDA) asserted jurisdiction over human
cloning and after Eve's birth investigated whether the alleged cloning violated
U.S. law. The FDA contended that its regulations forbid human cloning without
prior agency permission. At the time, the United States had no specific law
against human cloning.
In April 2001 Boisselier was investigated by a grand jury in Syracuse, New
York, after she testified before Congress that her company planned to clone a hu-
man. Parents of a baby boy who died at ten months were said to be the primary
financial backers of Clonaid. With plans to use the boy' s DNA to clone the dead
baby, Boisselier said, "My goal is, as it has always been, a very healthy baby. The
right of an individual to use his own genes as he wants is a basic human free-
dom. "
35
Not a medical doctor, Boisselier claimed two doctorates in chemistry and had
taught at Plattsburgh State University and Hamilton College in New York. She
was previously marketing director for a chemical company in France.
An Infamous Cloning Trio
Others made early news headlines with their announcement that they planned
to clone a human. Among these were a team of three controversial fertility
researchersRome-based embryologist Severino Antinori, director of the Inter-
national Research Institute in Italy, fertility researcher Panayiotis (Panos) Zavos,
director of the Andrology Institute of America in Lexington, Kentucky, and Is-
raeli physician Avi Ben-Abraham. The scientists said in early August 2001 that
they planned to clone humans. Antinori first gained notoriety by helping a sixty-
two-year-old woman have a child in 1994.
The three scientists told a panel at a scientific conference on human cloning
that they had recruited 200 infertile volunteers from different countries for their
cloning project. Like Boisselier, the investigators had relocated their laboratories
to undisclosed locations outside the United States.
In early April 2002 Antinori announced that he had cloned a human embryo,
which had been implanted into a surrogate mother. But a leading bioethicist and
outspoken critic of human cloning, Art hur Caplan, director of the Center of
Bioethics at the University of Pennsylvania Health System, called the announce-
ment "nothing more than hype and sizzle. . . . I don' t believe this is even practical.
They claim to have 200 couples lined up to bring to some remote location and per-
form IVF [in vitro fertilization] procedures using cloned cells and then take care of
all the pregnancies that might result. It just doesn' t sound plausible."
36
A Look Ahead
Scientists have done the job they were asked to do and there is now the technol-
ogy to clone a human. Yet, many fear human cloning, most likely because the
technology has progressed so far so quickly. Others, however, believe that the
only real threat is our own narrow complacency.
1 9 D
CLDNI NG A HUMA N
Much of the fear of human cloning appears similar to those of previous
breakthroughs. For example, there was a time when birth control was viewed as a
moral sin, in vitro fertilization was unthinkable, and heart transplants were
morally and ethically unacceptable. Even general surgery at one time was ob-
jected to on the grounds that it interfered with God' s creation.
Because animal cloning yields high failure rates, reproductive experts believe it
highly likely that human cloning would result in some birth defects, stillbirths,
and a high rate of miscarriages. All this has the potential to cause social night-
mares. Because of this no responsible U.S. scientist or public policy maker appears
to favor human cloning. There are some who say, however, that creating a human
clone is not all that difficult. They say that all that is needed is the same setup as
that used for in vitro fertilization and because of this, the risks are minimal.
Cloning of humans is at an ethical and moral crossroads, and most scientific
inquiries and bioethical conversation about human cloning are on the subject of
pro-life politics and religion. Human cloning is not prohibited by some religions
or by the Bible or the other holy texts of major religions. The fundamental con-
cern, as it has always been, centers around the moral status of the embryo.
Whereas abortion involves the termination of life, cloning involves the creation
of a new life.
It is now up to our politicians and society in general to determine whether
human cloning should be permitted and, if so, how it should be used. If human
cloning moves forward, we will need to protect the rights and dignity of any hu-
man beings who might result from cloning techniques by ensuring that good laws
are in place and that human cloning does not result in deformed individuals.
Writing for the Ethics Board of the Department of Health, Education, and Wel-
fare, Sid Leiman said, "If what is intended is the creation of human clones whose
organs would be designated for transplantation purposes, I fail to see by what
ethic or law any clone could be designated a donor rather than a recipient. And if
experiments are being undertaken whose intended result is the cloning of a hu-
man being, we had better legislate now regarding the rights and privileges of such
clones."
37
One cannot accurately predict what developments in human cloning will oc-
cur in the future, let alone when. However, it is wise to remember that what is not
acceptable today may well be in the near future.
This will demand that we look first to the past, and then to the present to de-
termine whether human cloning is beneficial for the future of our society. In so
doing, there are two important questions that need to be asked: Can we safely
clone humans? Should we clone humans?
1 9 1
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NDTES
Chapter 1. Recombining DNA Molecules
1. Watson 1968, 1.
2. Watson 1990, 44-49.
3. Watson and Crick 1953, 737-38.
4. Krimsky 1982, xiii.
5. Jackson, Symon, and Berg 1972.
6. Krimsky 1982, xiii.
7. Grody and Hilborne 1992, 166-71.
8. Zilinskas and Zimmerman 1986.
9. Chang and Cohen 1977, 4811-15.
10. Cohen 1977, 654-57.
l l . Rei nhol d 1969.
12. Glassman 1970, 963-64.
13. Beckwith 1970, 46-58.
14. Glassman 1970, 963-64.
15. Gershon 1983, 3-16.
16. Jackson and Stich 1979, 99-126.
17. Witt 1990.
18. Berget al . 1974,303.
19. Krimsky 1982.
20. Berget al . 1974,303.
21. Singer and Soil 1973.
22. Krimsky 1982.
23. Berget al . 1974,303.
24. Ibid.
25. Cohen 1977, 654-57.
26. Wade 1975.
NDTES
27. Gershon 1983, 3-16.
28. Sinsheimer 1978.
29. Berget al . 1974,303.
30. Berget al . 1975,991-94.
31. Emery 1984.
32. Zimmerman 1978, 273-301.
33. Chargaff 1976, 938-39.
34. Peattie 1995.
35. Singer 1976, 257-58.
36. Javits and Kennedy, quoted in Swazey, Sorenson, and Wong 1978, 1019-78.
37. Swazey, Sorenson, and Wong 1978, 1019-78.
38. Federal Register 1987, 49596-9609.
39. Nightingale, quoted in Sun 1982, 1079-80.
40. Baltimore, quoted in Sun 1982, 1079-80.
Chapter 2. Splicing Life: Technological Revolution or Pandora's Box?
1. Chargaff 1977, 32-35.
2. Zimmerman 1978, 273-301.
3. Chang and Cohen 1977, 4811-15.
4. Bender and Leone 1990.
5. Culliton 1990a, 974-76.
6. Culliton 1990b, 1373.
7. Miller 1990, 1368.
8. Swinbanks 1989, 398.
9. Roberts 1992, 677-78.
10. Brenner 1978, 2-3.
11. Watson 1978.
12. Emery 1984, 273-301.
13. Witt 1990.
14. Zilinskas and Zimmerman 1986.
15. Task Force on Human Life and the New Genetics 1982.
16. General Secretariats 1982.
17.Emanuel 1984, 266-69.
18. Ibid.
19. President's Commission for the Study of Ethical Problems in Medicine and
Biomedical Research 1982.
20. Ibid.
21. St i chl 978, 187-205.
22. Swinbanks 1989, 398.
23. Sharpies and Davis 1987, 1329-35.
24. Ibid.
25. Roberts 1992, 677-78.
26. Palca 1989, 398.
27. Zilinskas and Zimmerman 1986.
28. Mooney and Risser 1989, 297.
1 9 4
NOTES
Chapter 3. The Book of Life: The Human Genome Project
1. Netting and Wang 2001.
2. Dash 1991, 94.
3. Burke, Carle, and Olson 1987, 806-8.
4. Watson and CooloDeegan 1991, 8-11.
5. Sai ki et al . 1988, 487-91.
6.Jaroff 1989, 62-67.
7. CookT)eegan 1989, 661-63.
8. U.S. Congress, Office of Technology Assessment 1988.
9. Dulbecco 1986, 1055-56.
10. Pines 1986.
l l . Lewi nl 986, 157-60.
12. Alberts 1985, 337-38.
13. U.S. Congress, Office of Technology Assessment 1988.
14. DeLisi 1988, 488-93.
15. U.S. Congress, Office of Technology Assessment 1988.
16. Leder 1990, 1-3.
17. Annas 1989, 19-21.
18. Grisolia 1991, 404-5.
19. U.S. Department of Health and Human Services and U.S. Department of Energy
1991-95.
20. Watson 1990, 44-49.
21. U.S. Department of Health and Human Services and U.S. Department of Energy
1991-95, 5.
22. McKusick 1990, 73-74.
23. Collins and Galas 1993, 43-46.
24. Barnhart 1989, 651-60.
25. Watson 1989.
26. Watson 1990, 44-49.
27. Cantor 1990, 49-51.
28. Ferguson-Smith 1991, 61-65.
29. Ibid.
30. Barnhart 1989, 657-60.
31. McKusick 1989a, 910-15.
32. Bodmer 1991, 73-74.
33. Pinkel, Straume, and Gray 1986, 2934-38.
34. Licter, Tang, and Call 1990, 64-69.
35. St ernberg2001, 9A-B.
36. Lander, quoted in Sternberg 2001, 9A-B.
37. Jasny and Kennedy 2001, 1153.
38. Chan 2002.
39. Bush 2003.
Chapter 4. Laboratory Babies: New Biology, Old Morality
1. Warnock 1985a.
2. Englehardt 1986, 239-41.
3. Warnock 1985b, 4.
4. Edwards and Steptoe 1980, 115-16.
1 9 5
NOTES
5. Edwards 1965, 926-29.
6. Steptoe and Edwards 1970, 683-89.
7. Warnock 1984, 4.
8. Fishel 1988, 54-72.
9. Caplan 1986, 241-53.
10. Morris 2002.
11. Ostermeier 2002, 772-77.
12. Edwards, Steptoe, and Purdy 1980, 737.
13. Roberts and Lowe 1975, 498-99.
14. Hammond 1914, 263-77.
15. Robinson 1921, 137-51, 209-31.
16. Hertig and Rock 1949, 968-93.
17. Biggers 1981,336-42.
18. Goodman 2002.
19. Engelhardt 1986, 239-41.
20. Kass 1972.
21. Berg 1999, 293.
Chapter 5. The Warnock Report
1. Singer and Wells 1984.
2. Warnock 1985b, ix-x.
3. Ibid., 4.
4. Warnock 1984, 3.
5. Ibid., xiii.
6. Ibid., 6.
7. Spallone 1986, 544.
8. Editorial 1984a.
9. Warnock 1984, vi-vii.
10. Ibid., 10.
11. Editorial 1984b.
12. Ibid.
13. Warnock 1985b, 60.
14. Ibid., 61.
15. Spallone 1986, 543-50.
16. Warnock 1985b, xiv.
17. Ibid., 71.
18. Corea 1985.
19. Warnock 1985b, xvi-xvii.
20. Spallone and Steinberg 1987, 166-83.
21. Ibid., 170.
22. Warnock 1985b, xv.
23. Ibid., 67-68.
24. Warnock 1984, 5.
25. Spallone and Steinberg 1987, 172.
26. Warnock 1984b, 55.
27. Boyson 1978.
28. Warnock 1985b.
29. Ibid.
30. Ibid.
1 9 6
31. Warnock 1985b, 8.
32. Ibid.
33. Edwards and Steptoe 1980, 115-16.
34. Caplan 1986, 241-53.
35. Warnock 1985b.
36. Ibid.
37. Ibid.
38. Warnock 1984, 44, 67.
39. Ibid., 44, 45.
40. Editorial 1984b.
41. Edwards and Steptoe 1980, 115-16.
42. Spallone 1986, 548.
43. Editorial 1984b.
44. Warnock 1985b, 80-86.
45. Ibid., vii.
46. Caplan 1986, 241-53.
47. Sattaur 1984, 12-17.
48. Editorial 1985, 417.
49. Campbell 1984.
50. Warnock 1984, 10.
51. Ibid., 11.
52. Editorial 1984a.
Chapter 6. The Human Genome Diversity Project
1. Bowcock and Cavalli-Sforza 1991, 491-98.
2. Smith 1993. Cayuga and Onandaga leaders were suspicious of a scientific study
that wanted DNA samples from their nations.
3. Bowcock et al. 1991, 839-43.
4. Chi ul 991.
5. Cavalli-Sforza et al. 1991, 490-91.
6. Ibid.
7. Ibid., 491-98.
8. Greely and Cavalli-Sforza 1993.
9. King 1996. Allan Wilson' s group at Berkeley collected a different form of genetic
material known as mitochondrial DNA. Inherited over time, it was useful in tracking evo-
lutionary relationships. Wilson' s studies of mitochondrial DNA led him to the contro-
versial theory that all humans descended from a single woman who lived in Africa
200,000 years ago.
10. Cavalli-Sforza et al. 1991, 490-91.
11. Vigilant et al. 1990, 9350-54.
12. Stoneking et al. 1990, 717-33.
13. Stoneking and Wilson 1989, 215-49.
14. Smith 1993.
15. Johnson 1991, 44-48.
16. Greely 1993a.
17. Greely 1993b.
18. Chui l 991.
19. Cavalli-Sforza et al. 1991, 490-98.
NOTES
197
Chapter 7. The HGDP Debate
1. Cavalli-Sforza et al. 1991, 490-98.
2. Apodaca, quoted in Holland 1995.
3. Greely 1995a.
4. Harry 1994. Debra Harry is a Paiute Indian from Nevada who has researched is-
sues related to the HGDP.
5. Australian Genethics Network 1994.
6. Ibid.
7. Annas 1995.
8. Hammond 1995.
9. Greely 1993c.
10. Harry 1995.
11. Cayuqueo 1993.
12. Brown 1995.
13. Hammond 1995.
14. Greely 1995b.
15.Ibid.
16. Hammond 1995.
17. Greely 1995b.
18. Hammond 1995.
19. Greely 1995b.
20. Greely 1995c.
21. Friedlaender 1995.
22. Keohane 1995.
23. Mooney 1993.
24. Greely 1995c.
25. Christie 1995.
26. Ibid.
27. Swedlund, quoted in Brown 1993.
28. Tilton, quoted in Brown 1993. Brown served as project officer for the Central
Australian Aboriginal Congress.
29. Zalabata 1995.
30. Shenandoah, quoted in Bereano 1995.
31. Mooney 1993.
32. South and Meso American Indian Information Center (SAIIC) 1993.
33. Ibid.
34. Hammond 1995.
35. World Council of Indigenous Peoples (WCIP) 1993.
36. Indigenous Peoples of the Western Hemisphere 1995.
37. Ukupseni, Kuna Yala 1997.
38. Cordillera People's Alliance 1993.
39. Kreeger 1996, 1.
40. Butler 1997, 373.
41. Wadmanl 997, 774.
42. Smaglik2000, 912.
43. Macer 1999, 287-89.
44. Greely 2003.
NOTES
198
Chapter 8. Stem-cell Research
1. Fischer 2001, 52.
2. Somerville, quoted in Vergano 2001, 6D.
3. Lanza, quoted in Fischer 2001, 52-63.
4. Vergano 2001, 6D.
5. Begley 2002, 84-86.
6. Ibid.
7. Scholer 2003.
8. Lanza 2001b, 6D At the time, Dr. Lanza was Vice-President of Medical and Sci-
entific Development at Advanced Cell Technology, Inc. (ACT).
9. Vogelstein 2000. Dr. Vogelstein is a researcher at the Johns Hopkins University
School of Medicine.
10. West, quoted in Fischer 2001, 60.
11. Oderberg, quoted in Weise 2002b, 3A.
12. Fischer 2001, 54.
13. West, quoted in Fischer 2001, 57. Dr. West was an executive/researcher for ACT
and was considered a "visionary."
14. Fischer 2001, 57.
15. Ibid., 59.
16. Ibid., 57.
17. Ibid., 62.
18. Weise 2002a, 3A.
19. Ostermeier 2002, 772-77.
Chapter 9. A Major Decision
1. Bush 2001a.
2. Bush 2001b.
3. Bush, quoted in Lindlaw 2001.
4. Fleischer, quoted in Weise 2002c, 5D.
5. Duberstein and Deaver, quoted in Cloud 2001, 24. Duberstein was former Chief
of Staff for President Ronald Reagan.
6. Kass 2001. Dr. Kass is a University of Chicago biomedical ethicist. A conserva-
tive, he was appointed by President Bush to head a commission to oversee stem-cell re-
search.
7. Bush, quoted in Lindlaw 2001.
8. Pope John Paul II, quoted in Meckler 2001.
9. National Institute of Health 2001, 650.
10. Mohammed 2002.
11. Willing 2002.
12. Fiorenza2001.
13. Fiorenza, quoted in Keen 2001, 5A.
14. Robertson, quoted in Keen 2001, 5A. Robertson is founder of the Christian
Coalition.
15. National Right to Life Committee, quoted in Mohammed 2002.
16. Thompson 2001a, 14A. Thompson was U.S. Secretary of Health and Human
Services.
17. Bush, quoted in Page and Hall 2001, 4A.
18. Kennedy, quoted in Meckler 2001.
NOTES
199
19. Daschle, quoted in Kenen 2001.
20. Thompson 2001b. U.S. Secretary of Health and Human Services.
21. Weise 2002c, 5D
22. McKay, quoted in Weise 2002c, 5D. McKay is a senior investigator at the National
Institute of Neurological Disorders and Strokes at the National Institutes of Health in
Bethesda, Maryland.
23. Fleischer, quoted in Weise 2002c, 5D.
24. Caplan, quoted in Manning 2001, 8D
25. Caplan, quoted in Jacoby 2001, 14-16.
26. Thompson 2001a.
27. Bush, quoted in Ross 2001.
28. Frist, quoted in Ross 2001.
29. Kennedy, quoted in Ross 2001.
30. Specter, quoted in Ross 2001.
31. Daschle, quoted in Ross 2001.
Chapter 10. Reproductive Cloning
l . Beddi ngt onl 997.
2. Bouchard 1997, 52-57. Bouchard is a professor of psychology at the University
of Minnesota in Minneapolis. He was president of the Behavior Qenetics Association from
1993 to 1994.
3. Ibid.
4. Di Berardino and McKinnell 1997, 32-37. Di Berardino is Professor Emerita of
Biochemistry at the Medical College of Pennsylvania-Hahnemann School of Medicine,
Allegheny University of the Health Sciences in Philadelphia. McKinnell is a professor of
genetics and cell biology at the University of Minnesota in St. Paul. Both authors are con-
sidered experts on the cloning of normal and cancerous frog cells.
5. Gurdon 1997, 26-31. Gurdon was chair of the Wellcome Trust/Cancer Research
Campaign Institute at the University of Cambridge in England.
6. Ibid.
7. Ibid., 29.
8. Ibid.
9. Ibid., 26-31.
10. Ibid., 30.
11. Ibid., 26-31.
12. Lutz 1997, 10-11.
13. Di Berardino and McKinnell 1997, 32-37.
14.Ibid.
15. Beddington 1997.
16. Hart, Turturro, and Leakey 1997, 47-62. Hart is a biogerontologist. Turt urro is a
biologist and biophysicist. Leakey is a biochemist at the National Center for Toxicologi-
cal Research in Jefferson, Arkansas.
17. Ibid., 51.
18. Ibid.
19. Fischer 2001, 52-63.
20. Hart, Turturro, and Leakey 1997, 47-62.
21. Wolf 1997, 1. Wolf is senior scientist at the Oregon Regional Primate Research
Center.
22. Beddington 1997.
NOTES
200
NDTES
23. Kitcher 1997, 58-62.
24. Fischer 2001, 52-63.
Chapter 11. Cloning a Human
1. Levin 1976.
2. Rorvik 1978.
3. Parens, quoted in Lutz 1997, 10-11.
4. Dixon 1993.
5. Dixon 1997.
6. Ibid.
7. Weiss 2002, A04.
8. Ribalow 1997, 38-42.
9. Di Berardino, quoted in Kiernan 1998, A40-41.
10.Ibid.
11. Purcell and Gould 1997, 14-15.
12.Ibid.
13. Purcell and Gould 1997, 16.
14.Ibid.
15. Will 2001.
16.Ibid.
17. Thomas 2000.
18. Fitzgerald, quoted in Thomas 1991.
19. Bilger 1997, 17.
20. Ibid., 18.
21. Clinton, quoted in Ross 1997.
22.Ibid.
23. Clinton, CNN Interactive 1997.
24. Di Berardino, quoted in Kiernan 1998, A40-41.
25. Walters 2001, 9-11.
26. Cohen 1999, 7.
27. Wilmut, quoted in Bilger 1997, 17-19.
28. Ibid.
29. Ibid.
30. Kiernan 1998, A40-41.
31. Baltimore, quoted in Kiernan 1998, A40-41.
32. Pope John Paul II, quoted in Associated Press 2001. Meeting with President
George W. Bush.
33. Singer, quoted in Friend 2002, 5D.
34. Boisselier, quoted in Willing 2001b.
35. Ibid.
36. Caplan, quoted in Friend 2001, 5D.
37. Lei man2001.
2 D1
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2 1 D
I NDEX
Abr am, Mor r i s B., 19, 26-27
ABS Gl obal , Inc., 172
Acost a, Isidro, 111
ACT. See Advanced Cell Technol ogy Inc.
(ACT)
action groups, 20-22, 27-29
Adams, Mark, 41
adult-cell cloning, 161, 166-67, 172
Advanced Cell Technol ogy Inc. (ACT),
138-40, 150, 172, 180
aging and genetic research, 133-34, 167-68
Al bert s, Bruce, 39
Ameri can Associ at i on for t he Advancement
of Science (AAAS), 154
Ameri can Life League, 151
Ameri can Society of Reproduct i ve
Medicine, 139
Ammash, Hudah, 32
Amp l i Chi p CYP450, 30
ANDI , 182
angiogenesis, 142
animals: cloning of, 159-60, 162-73, 180,
182, 191; st em cells and, 141;
transgenic, 171-73
Annas, George, 109
annot at i on, 49
Ant i nor i , Severino, 190
Apodaca, Ray, 106
artificial i nsemi nat i on (AI), 62, 79-80
Asi l omar Conferences, 7, 9-12, 31
"Baby M" case, 63
bacteria, 8, 17, 22- 23, 28; genomes and, 36,
42, 50. See also E. Coli
Baltimore, David, 8, 15-16, 37, 188
Barrell, Bart, 37
Becker muscul ar dystrophy, 37
Beckwith, Jonat han, 6
Ben-Abraham, Avi, 190
Berg, Paul, 6-10, 38
Biggers, J. D. , 64-65
Biodiversity Convent i on, 111, 118, 126
bi ohazards of r DNA, 5-18
biological warfare, 5, 31- 33, 107, 125
Biological Weap ons Convent i on, 33
bi omedi ci ne, 51. See also diseases, di sorders
and genetic research
biopiracy, 108-9
BiPolis research center, 135
blastocysts, 64, 135-37
blastulas, 163
Blattner, Fred, 42
bl ood vessels and st em cells, 142
Bodmer, Julia, 95
Bodmer, Walter, 80, 95
body cell cloning. See somatic cell cloning
Boisselier, Brigitte, 184, 189-90
Book of Life. See Human Genome Project
Bost on In Vi t ro Fertilization, 142
Botstein, David, 36- 37, 37
Bouchard, Thomas, 200n2
Boyer, Herbert , 7, 22-23
Boys from Brazil, The, 176
Boyson, Rhodes, 79
Brave New World (Huxley), 55-56
Brazilian Society of Bi ochemi st ry and
Mol ecul ar Biology, 41
Brenner, Sydney, 22
Briggs, Rober t , 163
British Medi cal Associ at i on (BMA), 73, 84
Brown, Louise, 57-59, 64
Brown, Patrick, 42
Brown, Ron, 110, 113-14
Bush, George W., 51, 143; reaction t o
decision of, 150-53; st em cell research
a nd, 145- 51, 152, 155
Califano, Joseph, 22
Callahan, Daniel, 20, 22
Cambri dge, City of, 12-13
Campbel l , Allan, 15-16
Campbel l , Keith H. S., 165-68
cancer, 6, 8, 17, 38
Cant or, Charles, 95
Capl an, Art her, 154, 190
Card, Andrew, 148
Carter, Jimmy, 25
Cavalli-Sforza, Luigi Luca, 93- 98, 104-5,
126
Cayuqueo, Nilo, 112-13
cDNA. See compl ement ar y DNA
Celera Genomi cs, 43
cell lines: commerci al i zat i on of, 124;
patents, 110-19; stem, 141, 146-48,
153-55
cells: cumul ous, 169;
differentiated/specialized, 165-68;
mul t i pot ent adult progeni t or (MAPCs),
134. See also st em cells
Cent ral Australian Abori gi nal Congress
(CAAC), 102
Chakrabart y, Ananda, 22- 23, 109
Chan, Eugene, 51
Chang, S., 20
Chargaff, Erwi n, 3, 11-12, 20
Chri st i an Legal Society (CLS), 156
Christie, Jean, 111, 118
chr omosomes, 36, 50, 60- 61, 99-100; maps
and sequencing of, 22, 40, 42- 43, 49
Chur ch, George, 37
churches. See religions and genetic research
Cibelli, Jose, 140
Cl i nt on, William, 29, 44, 149-50, 184-86
Cl onai d, 184, 189-90
cloning, 48, 74; animal, 159-60, 162-73,
180, 182, 191; combi ni ng species and,
161, 182; embr yos and, 136-38, 141,
143, 147, 162; hi st ory of, 162-68;
human (see human cloning); ki nds of,
161-62; in nat ure, 160; reproduct i ve,
159-73; stem cell, 132, 162; therapeutic,
135-36, 162
Cohen, Daniel, 42
Cohen, Jonat han, 187
Cohen, S. N. , 20, 22-23
Cohen, Stanley, 7, 10
Col d Springs Har bor Laborat ory meetings,
38-40
Collins, Francis, 42- 44, 49
commercialization, 65-66, 83-84, 109, 119,
124, 178
Commi ssi on for t he St udy of Ethical
Probl ems in Medi ci ne and Biomedical
and Behavioral Research, 25-27
Commi t t ee of Inqui ry i nt o Huma n
Fertilization and Embr yol ogy in t he
Uni t ed Ki ngdom, 57; r epor t of, 71-90
commodi fi cat i on, 65-66, 111, 116, 151
compl ement ar y DNA, 42, 48
concept i on, 63, 136, 138, 147
Conradi , Wilco, 133
cont ai nment , 10, 1416
cont roversy: decade of, 4- 7; HGDP and,
105-28; over cloning, 176-91; over in
vitro fertilization, 57-59, 62- 69; r DNA
and, 20- 33, 27-29; st em cell research
and, 129, 136-39, 142-43, 148-53;
surrogacy and, 62- 63. See also
envi ronment al concerns; ethical
concerns; political debates
Cook-Deegan, Rober t , 95
Cordillera People' s Alliance, St at ement of,
125-26
Crick, Francis, 3
cryogenic preservat i on (cryopreservation),
61, 67. See also freezing
cytogenetic maps, 49
Daschle, Tom, 153, 156
Dauset t , Jean, 40
Davies, David, 84
Davis, Bernard D , 28-29
INDEX
212
Davis, Gray, 142
Davis, Ronal d, 36
Deaver, Michael, 148
DeLisi, Charles, 39
Dep ar t ment of Agriculture, 38
Dep ar t ment of Energy (DOE), 38-42, 45
"designer bugs, " 32
diabetes, 99-100, 133, 172
Diagnostic Devel opment Branch, 46
Diamond vs. Chakrabarty, 23
Di Bernardi no, Marie, 164-65, 186, 200n4
Dickey, Jay, 149-50
diseases, di sorders and genetic research,
98-102, 104, 131-35, 141-42; bl ood
vessels and, 142; diabetes and, 99-100,
133, 172; eyes and, 135; heart repair
and, 133; neur ons and, 133; teeth and,
134-35
di sequi l i bri um, genetic, 100
diversity, 155, 181-82; Project, Human
Genome (HGDP), 93-104; prot ect i on
of bio, 105
Di xon, Patrick, 179
DNA: cloning and, 48, 161-62;
compl ement ar y (cDNA), 42, 48;
ethnicity and, 93-94; foreign, 48, 50; in
human genome, 35; j unk, 50;
mi t ochondri al , 99, 197n9; pol ymerase
chain reaction (PCR), 37, 48-49;
recombi ni ng (rDNA), 3-18; sampling,
103-4; sequencing, 36, 48- 49, 99; and
stem cell research, 141. See also Human
Genome Project
DOE. See Dep ar t ment of Energy (DOE)
Dolly (cloned sheep), 165-68
Donis-Keller, Helen, 37
dopami ne and st em cells, 133
"doubl e effect," 78
doubl e helical st ruct ure, 3
Driesch, Adol p h Eduard, 162
Duberst ei n, Kennet h, 148, 199n5 (chap. 9)
Duchenne muscul ar dystrophy, 37, 48
Dul becco, Renat o, 38
E. Coli, 6, 10, 15, 20; genome, 36-37, 42, 49
ecological communi t i es, 28-29
Edgar, Bob, 48
Edwards, Rober t , 58, 64, 80, 84
eggs: donat i on of, 60- 61, 65, 81-82, 176; as
property, 65- 68; from st em cells, 134
Elsdale, Thomas R., 163
embryobl ast , 64
embryos, 64-69; cloning of, 136-38, 141,
143, 147, 162; donat i on of, 82- 83; and
t he law, 76-78; leftover ("spare"), 64,
66-67, 77, 81, 137-38; loss of, 64- 65,
89; as property, 65- 68; research on, 65,
74-78, 90; sources of, 136-37; stems
cells and dest ruct i on of, 132, 136-37,
148-50, 152
endangered species cloning, 171
ensoul ment , 64, 186
envi ronment al concerns, 28-29, 32-33
Ethical, Legal, and Social Issues (ELSI)
Branch, 45, 99
ethical concerns: cloning and, 183, 186-87,
191; and genome research, 40- 41; and
r DNA, 5-18, 23-27; in vitro
fertilization and, 58-59, 63-69, 75, 78;
in War nock Report , 71-90. See also
cont roversy
et hni c cleansing, 183
ethnicity and genetic variants, 93-94
et hnoci de, 126
eugenics, 21, 126, 182-84
European government and organizations,
47, 96, 111, 188
evol ut i on: and DNA, 94- 95, 97- 98; t wo
lines of, 50
expl oi t at i on: of i ndi genous peoples, 96,
100-101, 105-8, 113, 119, 125, 197n2;
of pl ant and animal genes, 108
Fauci, Ant hony, 43
federal funding and research, 139, 145-50,
153-54
Federal Interagency Advi sory Commi t t ee on
Recombi nant DNA Research, 15
Federat i on of Ameri can Scientists (FAS), 21
Fel dman, Marc, 95, 97
feminist concerns, 75, 77, 79, 81, 90
fertility clinics, 65-66, 72
fertilization, in vi t ro (IVF), 55-69
field testing, 28-29
Fiorenza, Joseph A. , 151
First, Neal, 165
Fischberg, Michael, 163
Fitzgerald, Kevin, 184
Fleischer, Ari , 148, 154
Fl ei schmann, Rob, 42
Food and Dr ug Admi ni st r at i on (FDA), 29,
190
Ford, Gerald, 15
Foundat i on on Economi c Trends, 27-29
Fox, Michael J., 141
Franklin, Rosalind, 3
INDEX
213
Fraser, Claire, 41-42
Friedlaender, Jonat han, 114
Frist, Bill, 150, 155
frozen semen, eggs and embryos, 61, 84- 85,
136, 166-67
fruit flies: cloning of, 164; genome, 36,
43- 44, 50
funds: diversion of and HGDP, 108-9;
research and federal, 139, 145-50,
153-54
Gaj dusek, Carl et on, 115
Gal t on, Francis, 183
gastrulas, 163
GATT. See General Agreement of Tariffs
and Trade (GATT)
Gearhart , John D, 132-33
GenBank database, 42
General Agreement of Tariffs and Trade
(GATT), 111, 126
General Electric Cor p or at i on, 109
genes: maps of, 44; muscul ar dystrophy, 37;
shuffling of, 36; splicing of, 19-33, 183
(see also recombi ni ng DNA)
gene therapy prot ocol s, 28-29
"genetic deat h, " 59-60
genetic di sequi l i bri um, 100
genetic engineering, 12-13, 18, 23-26,
27-28, 179, 188; of animals, 172-73.
See also recombi ni ng DNA
genetic flaws, repair of, 52
genetic i nformat i on, 21, 50-51
Genet i c Mani pul at i on Advi sory Gr oup
( GMAG) , 22
genetic maps, 49. See also mappi ng
Genet i c Savings and Cl one, 170-71
genetic tests, 30
genocide: genetics and, 119. See also
et hnoci de
genomes, 36-37, 42-44; genes in human,
49-50; Project, Human, 35-52
genomi c regions, 100
Germany, 18; Nazi, 183
Ger on Cor p or at i on, 141, 147
Gi l bert , Walter, 13, 36-38
Goodman, Ellen, 67-68
Gor don Research Conference on Nucleic
Acids, 7-8
Got t esman, Susan, 16
Goul d, St ephen Jay, 182
Greeley, Henr y: and HGDP debate, 109-18,
126-28; and HGDP format i on, 93, 96,
98, 103
Greenberg, Judi t h, 126
Greengross, Wendy, 84
Guaymi General Congress, 111
Guaymi pat ent , 110-13
Quidelines for Research Involving Recombinant
DNA Molecules (NIH), 10
Gur don, John, 163-65, 200n5
Hagahai people, 115
Hall, Jerry, 186
Hammond, Edward, 109, 115, 117
Harry, Debra, 198n4
Hart , Ronal d, 200nl 6
Haseltine, William, 41, 43
Hastings Center, 20-22
Hayashizaki, Yoshide, 42
hazards of r DNA, 5-18
Heal t h and Envi ronment al Research and
Advi sory Commi t t ee (HERAC), 39
Healy, Bernadine, 29, 41
Hecht vs. Superior Court, 65-66
Hennen, Sally, 164
HGDP. See Human Genome Diversity
Project (HGDP)
HGP. See Human Genome Project (HGP)
Hitler, Adolf, 176, 183
Hol ocaust , 183
Hood, Leroy, 37
Hoppe, Peter, 159
Howard Hughes Medi cal Inst i t ut e (HHMI ) ,
38-39, 142
HTLV viruses, 110-11, 115
Hudson, Thomas, 42
HUGO. See Human Genome Organi zat i on
( HUGO)
human cloning, 175-91; alleged success in,
189-90; ban on, 150- 51; Bush and,
146-47, 155; diversity issues and,
181-82; eugenics and, 182-84; failure
rates and, 180-81, 191; good and bad
of, 176-82; growing organs and, 180;
headless, 179-80; " human banks " and,
179; op p onent s of, 180-82, 184-86,
188-89; p r op onent s of, 177-79,
. 181-83, 188; twins and, 160, 182
Human Embr yo Research Panel, 65
Human Eugenics Advi sory Commi t t ee, 21
Human Gene Therapy Subcommi t t ee
(HGTS), 28
Human Genome Analysis Pr ogr amme
(HGAP), 47
Human Genome Diversity Project (HGDP),
93-104; calls for a halt to, 119-26;
INDEX
214
concerns of i ndi genous peoples about ,
106-9, 112-13; current status of,
127-28; debat e over, 105-28; defense
of, 116-18; et hni c hi st ory and, 93-94;
funding and, 108-9, 127; hi st ory of,
94-96; human rights and, 106-7, 113,
119-20, 122, 124; i nformed consent
and, 104, 107, 117-18, 125;
i nt ernat i onal wor kshops for, 96-97;
NRC panel on, 126-27; pat ent s and,
108-19; popul at i ons for, 102-3, 117;
sampling and, 103-4; value of, 97-102
Human Genome Educat i on Program
(HGEP), 46
Human Genome Educat ors Program, 46-47
Human Genome Initiative, 39-40
Human Genome Mappi ng Project (HGMP) ,
47
Human Genome Organi zat i on ( HUGO) , 41,
47- 48, 118; HGDP and, 95-97, 127
Human Genome Project (HGP), 35-52; feud
within, 43-44; foundat i on of, 36-37;
funding of, 45; goals of, 44- 45; hi st ory
of, 37- 43; i mpact of, 51-52;
i nt ernat i onal centers and programs,
47- 48; mappi ng and sequencing in,
48-49; results and surprises of, 49-50;
U.S. centers and programs, 45-47
human life, beginning of, 63-64, 136-38,
147
human rights: and genetics, 99; and
indigenous peoples, 106-7, 113,
119-20, 122, 124
Hussein, Saddam, 32
Huxley, Al dous, Brave New World, 55-56
Illmensee, Karl, 159
indigenous peoples: declarations and
resol ut i ons of, 120-26; expl oi t at i on of,
96, 100-101, 105-8, 113, 119, 125,
197n2; as focus of HGDP, 93-104;
genetic t echnol ogy and, 122-23; and
HGDP debate, 105-28; number s of, 94;
pat ent s and, 108-19, 122; Worl d
Congress of, 109, 112-13, 119-21
infertility, 59-60, 69, 74-75, 80-81
Infingen Inc., 172
informed consent : and HGDP sampling,
104, 107, 117-18; "i ndi vi dual consent "
and, 125; and reproduct i ve
technologies, 59, 77-78, 147
inheritance, 67- 68, 79, 85
Inqui ry Commi t t ee. See War nock Rep or t
Institute for Genomi c Research (TIGR), 41
Institute of Medical Research (PNG),
114-16, 118
insulin and st em cells, 133
interest/action groups, 20-22, 27-29
Int ernat i onal Mouse Mutagenesis
Consor t i um, 36
intracytoplasmic sperm injection, 61
in vi t ro fertilization (IVF), 55-69; infertility
and, 59-60; responses to, 59, 68;
t echni ques of, 60-62, 82; War nock
Rep or t and, 75, 80- 81; worl d' s first,
57-59
"isolates of historic interest, " 105, 126
IVF. See in vitro fertilization (IVF)
Jacob, Francois, 37
Japan, 42
Javits, Jacob, 15
Jenkins, Carol , 115-16, 118
Jewish faith, 151, 186
Joint Genome Institute, 42
Jonas Institute for Reproduct i ve Medicine,
142
Kass, Leon, 135, 148-49, 199n6 (chap. 9)
Kelly, Bishop Thomas, 23
Kennedy, Edward, 10, 15, 20, 152-53,
155-56
Keohane, Jeff, 116
Kidd, Kennet h, 95
King, Mary-Claire, 95, 98- 101, 126
King, Thomas J., 163
Klausner, Richard, 43
l aborat ory babies, 55-69
Lairmore, Michael, 110
Lander, Eric, 42- 43, 50
Lanza, Robert , 131, 140, 199n8 (chap. 8)
Laskey, Ronal d A. , 164-65
Lawrence Berkeley Nat i onal Laboratory,
46-47
Leahy, Patrick, 153
Leakey, Julian, 200nl 6
legal issues, 63, 65- 68, 76-78, 84
legislation and regulation, 21-22; cloning
and, 185, 188; current efforts toward,
155-56; embr yo dest ruct i on and,
149-50; scientists' responses to, 11, 20,
90, 153-54; on surrogacy, 84. See also
War nock Rep or t
Leiman, Sid, 191
Li pscomb, William, 16
INDEX
215
Los Al amos Nat i onal Laboratory, 38
Ludwig, Bob, 48
Mammal i an Genomi cs Branch, 46
Mandel baum, Rabbi Bernard, 23
mappi ng, 37, 44- 45, 48-49; of hi st ory of
civilization, 101
Mappi ng Project of HGP, 48- 49
Mappi ng Technol ogy Branch, 46
Maxam, Allan, 36
Mayo, Frederico, 40-41
McCl i nt ock, Barbara, 36-37
McGr at h, James, 165
McKay, Ronal d, 154, 200n22 (chap. 9)
McKi nnel l , Robert , 200n4
McLaren, Anne, 77
Medi cal Research Counci l (MRC), 47, 73
Medi ci ne, Ethics, and Society forum, 56-57
Mendel , Gregor, 52
Mergen, Bernard, 159
Mert z, Janet, 6
mice: cloning of, 159-60, 165, 169; genome
of, 36, 43
Midgely, Mary, 175
migrations and DNA, 94- 95, 97- 98, 101-2
Monad, Jacques, 37
Mooney, Pat Roy, 110-11, 116, 120
morat ori a, 7-10, 13, 21-22, 27, 40, 122, 186
Mount Sinai Hospi t al (Toront o), 108
Murray, Jeffrey, 42
muscul ar dyst rophy genes, 37
myelin and st em cells, 133
Nat i onal Academy of Sciences, 22, 39, 127,
154-55, 189
Nat i onal Bioethics Advi sory Commi ssi on
(NBAC), 29, 184-85
Nat i onal Cent er for Human Genome
Research ( NCHGR) , 40, 42, 45
Nat i onal Counci l of Chur ches Task Force,
23-25
Nat i onal Human Genome Research
Institute, 42
Nat i onal Institutes of Heal t h (NIH): embr yo
research and, 65, 185; guidelines, 10,
14-17, 28, 139; HGP and, 38- 43,
45-46; NCHGR, 40, 42, 45; pat ent s
and, 109, 115-16, 118; RAC, 9- 11,
21-22, 25, 28-29; st em cells and, 150,
153-54
Nat i onal Research Counci l (NRC), 39,
126-27, 173
Nat i onal Right t o Life Commi t t ee, 151
Nat i onal Science Foundat i on (NSF), 38
nat ural law, 186
NCHGR. See Nat i onal Cent er for Huma n
Genome Research ( NCHGR)
neur ons and st em cell research, 133, 187
Nexia Biotechnologies Inc., 171
Nightingale, Elena, 16
NI H. See Nat i onal Institutes of Heal t h
Noller, Harry, 48
Nor t h- Sout h Genome Conference, 41
NRC. See Nat i onal Research Counci l (NRC)
nuclear transfer/transplant, 135-36, 163-69,
185
Oderberg, David, 139
Office of Technol ogy Assessment (OTA), 39
Ol son, Maynard, 41
Onandagas, 102-3
oopl asmi c transfer, 141
"op er on, " 37
Orr, Nancy Hoffner, 165
Ort i z, Deborah, 142
ova. See eggs
Paabo, Svante, 95
Page, David, 42
Papua New Gui nea Patent, 114-19
Parens, Eric, 179
parental rights and responsibilities, 25, 79
part henogenesi s, 140
pat ent s: cell line, 110-19; Guaymi , 110-13;
i ndi genous peopl es and, 108-19, 122,
124-25; life forms and, 22- 23, 109;
Papua New Gui nea, 114-19; Sol omon
Islands, 113-14
Patrinos, Aristides, 44
Peattie, Debra, 12-13
pedigree analysis, 37, 44
Pena, Sergio, 41
Perry, Dan, 153
p er sonhood, 63-64, 74-75
pets and cloning, 170-71
Phi l i p p i ne Solidarity Gr oup of Tor ont o,
The (PSG), 126
physical maps, 49
Piazza, Al bert o, 95
Plunkee, Guy, 42
Points to Consider document s, 28-29
political debates, 20- 23, 27-29, 142-43,
155-56, 188-89
Pollack, Robert , 6
pol ymerase chain reaction (PCR), 37, 48- 49,
99
INDEX
216
Pope John Paul II, 149, 188
popul at i ons: DNA and hi st ory of, 98,
101-2; for HGDP, 102-3, 117;
indigenous, 94, 100-101
p ost humous reproduct i on, 65-68, 79, 84
PPL Therapeut i cs PLC, 172
prei mpl ant at i on analysis, 137
pri mogeni t ure, 79, 84
privacy and reproduct i on, 66
proteins, 50, 164
prot ocol s, 28-29, 101
Pseudomonas bacteria, 22- 23, 28, 50
public policy issues: Asi l omar Conference
and, 31; cloning and, 185-86, 188-89,
191; commi ssi ons and, 25-27, 29,
184-85; interest/action groups and,
20-22; r DNA and, 19-33; stem cell
research and, 142-43, 145-56. See also
controversy; political debates
Question of Life, A (Warnock), 72
RAC. See Recombi nant DNA Mol ecul e
Program Advi sory Commi t t ee (RAC)
racism, 102, 107
RAFI. See Rural Advancement Foundat i on
Int ernat i onal (RAFI)
Randall, Claire, 23
r DNA. See recombi ni ng DNA
Reagan, Nancy, 148
Recombi nant DNA Mol ecul e Program
Advi sory Commi t t ee (RAC), 9- 11,
21-22, 25, 28-29; guidelines, 10, 14-17,
28
recombi ni ng DNA (rDNA), 3-18; academic
involvement in, 12-13; argument s for
and against, 27; Berg letter on, 9;
commi ssi ons on, 25-27, 29;
conferences on, 7-12, 14; cont ai nment
and, 10; cont r i but i ons of, 30;
cont roversy over, 4- 7, 20-25, 27-29;
discovery of, 7; safety guidelines for, 10;
social implications of, 30- 31; Thi rd
Worl d and, 31
Red, Scot, 151
Reeve, Chri st opher, 141-42
Reeves, Raymond, 164-65
regulation. See legislation and regulation
rejection, i mmune system, 139
religions and genetic research, 23- 25,
111-12, 136, 138, 149, 151-52, 186-87
Religious Coal i t i on for Reproduct i ve
Choice, 151-52
Report of the Committee of Inquiry into Human
Fertilization and Embryology in the
United Kingdom, 57, 71- 90
reproduct i on: p ost humous, 65- 68, 84;
privacy and, 66
reproduct i ve cloning, 15973
reproduct i ve technologies: artificial
i nsemi nat i on (AI), 79-80; egg donat i on,
60- 61; frozen semen, eggs and
embryos, 61, 84- 85; i nformed consent
and, 59, 77-78; inheritance and, 67- 68,
79, 85; sperm banks, 61; surrogacy,
61- 63; t echni ques of, 60-62, 82; in
vitro fertilization (IVF), 55-69;
War nock Repor t on, 71-90
"rest ri ct i on endonucl eases, " 4
Rifkin, Jeremy, 21-22, 27-29
Rober t son, Pat, 151, 199nl 4 (chap. 9)
Robl , James M. , 140
Roman Cat hol i c Chur ch, 136, 138, 151-52;
Instruction on Respect for Human Life,
186
Rorvi k, David, 176
r oundwor m (nematode) genome, 36, 43, 49
Rove, Karl, 148
Rubi n, Gerald, 44
Rural Advancement Foundat i on
Int ernat i onal (RAFI), 108-11, 115-20
SAIIC. See Sout h and Meso Ameri can
Indi an Informat i on Cent er (SAIIC)
Sanger, Frederick, 36, 48
Scholer, Hans, 134
Science for t he People, 6
Scientific Coordi nat i ng Commi t t ee (SCC),
41
Seed, Richard, 187
Sequana Therapeutics, 108
sequencing, 42-44, 48-49, 99
Sequencing Technol ogy Branch, 46
severe combi ned immunodeficiency (SCID),
133
Shand, Hope, 126-27
Shapiro, Harol d, 169, 184
Shapiro, James, 5-6
Sharpe, Paul, 134-35
Sharpies, Frances E., 28-29
Shaw, Chri st opher, 187
Shenandoah, Leon, 119
Shin Yong Moon, 135
sickle-cell anemia, 30
Singer, Maxine, 8, 14, 189
Siniscalco, Marcello, 95
INDEX
217
Sinsheimer, Robert , 10, 37, 48
Skolnick, Mar k, 36
Smi t h, Chris, 156
Smi t h, Hami l t on, 42
social implications: of genome research,
40- 41; of r DNA, 30-31
Society for Social Responsibility in Science
(SSRS), 21
Soil, Dieter, 8
Sol omon Islands pat ent , 113-14
Solter, David, 165
somat i c cell cloning, 161, 166, 169, 176, 185
Somerville, Judson, 131
Song Chang-hun, 143
Sout h and Meso Amer i can Indi an
Informat i on Cent er (SAIIC), 106, 120
Sout her n Baptist Convent i on, 187, 189
Specter, Arl en, 156
Sp emman, Hans, 162
sperm, donat ed, 61; i nheri t ance and,
67- 68, 79, 85; as property, 65-68
Splicing Life (Carter Commi ssi on), 25
splicing of genes, 19-33
Stanford University, 141-42
st em cell research, 131-43; on animals, 141;
benefits and breakt hroughs of, 131-35,
141-42; Bush decision on, 145-56;
debat e over, 138-39; federal funding
and, 139, 145-50, 153-54; leaders in,
139-41; op p onent s of, 132, 138,
149-51; overseas, 143; sup p or t er s of,
149-50, 152-55
st em cells: adult, 134-35; cloning and, 132,
162; embryoni c, 131-37; lines of, 141,
146-48, 153-55; obtaining, 136-37
Steptoe, Patrick, 58, 64, 84
Stevenson, Adl ai , 20
Sul st on, John, 37, 41, 43
surrogacy, 61- 63, 83-84
SV40 virus, 6
Swedl und, Al an, 118
Takebe, Hi raku, 127
Taul i -Corpuz, Victoria, 105
telomeres, 140, 167-68
"test t ube" babies, 55, 57-58
Thomas, Cal, 183
Thomp s on, James, 141
Thomp s on, Tommy, 148, 150, 152-55
Ti l t on, Edward, 118-19
transgenic animals, 171-73
t rophobl ast , 64
Tung, T. C , 164
Tur t ur r o, Angelo, 200nl 6
Ukup seni , Kuna Yala, Decl arat i on of, 124
UNESCO, 40- 41, 127
Uni t ed Ki ngdom, 47, 143; War nock Rep or t
of, 71-90
Uni t ed Nat i ons Educat i on, Scientific, and
Cul t ural Organi zat i on. See UNESCO
U.S. Congress, 10, 22, 39-40, 45; cloning
and, 187-89; st em cell research and,
149-50, 155-56
U.S. government . See individual departments
and agencies
ut eri ne lavage, 82-83
"Vampi re Project, " 105. See Huma n
Genome Diversity Project (HGDP)
Varmus, Harol d, 155, 188-89
Ventor, Craig, 41-44, 49
Verfaillie, Cat heri ne, 134
Vogelstein,